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Experiment Definition in Science – What Is a Science Experiment?

In science, an experiment is simply a test of a hypothesis in the scientific method . It is a controlled examination of cause and effect. Here is a look at what a science experiment is (and is not), the key factors in an experiment, examples, and types of experiments.

Experiment Definition in Science

By definition, an experiment is a procedure that tests a hypothesis. A hypothesis, in turn, is a prediction of cause and effect or the predicted outcome of changing one factor of a situation. Both the hypothesis and experiment are components of the scientific method. The steps of the scientific method are:

• Make observations.
• Ask a question or identify a problem.
• State a hypothesis.
• Perform an experiment that tests the hypothesis.
• Based on the results of the experiment, either accept or reject the hypothesis.
• Draw conclusions and report the outcome of the experiment.

Key Parts of an Experiment

The two key parts of an experiment are the independent and dependent variables. The independent variable is the one factor that you control or change in an experiment. The dependent variable is the factor that you measure that responds to the independent variable. An experiment often includes other types of variables , but at its heart, it’s all about the relationship between the independent and dependent variable.

Examples of Experiments

Fertilizer and plant size.

For example, you think a certain fertilizer helps plants grow better. You’ve watched your plants grow and they seem to do better when they have the fertilizer compared to when they don’t. But, observations are only the beginning of science. So, you state a hypothesis: Adding fertilizer increases plant size. Note, you could have stated the hypothesis in different ways. Maybe you think the fertilizer increases plant mass or fruit production, for example. However you state the hypothesis, it includes both the independent and dependent variables. In this case, the independent variable is the presence or absence of fertilizer. The dependent variable is the response to the independent variable, which is the size of the plants.

Now that you have a hypothesis, the next step is designing an experiment that tests it. Experimental design is very important because the way you conduct an experiment influences its outcome. For example, if you use too small of an amount of fertilizer you may see no effect from the treatment. Or, if you dump an entire container of fertilizer on a plant you could kill it! So, recording the steps of the experiment help you judge the outcome of the experiment and aid others who come after you and examine your work. Other factors that might influence your results might include the species of plant and duration of the treatment. Record any conditions that might affect the outcome. Ideally, you want the only difference between your two groups of plants to be whether or not they receive fertilizer. Then, measure the height of the plants and see if there is a difference between the two groups.

Salt and Cookies

You don’t need a lab for an experiment. For example, consider a baking experiment. Let’s say you like the flavor of salt in your cookies, but you’re pretty sure the batch you made using extra salt fell a bit flat. If you double the amount of salt in a recipe, will it affect their size? Here, the independent variable is the amount of salt in the recipe and the dependent variable is cookie size.

Test this hypothesis with an experiment. Bake cookies using the normal recipe (your control group ) and bake some using twice the salt (the experimental group). Make sure it’s the exact same recipe. Bake the cookies at the same temperature and for the same time. Only change the amount of salt in the recipe. Then measure the height or diameter of the cookies and decide whether to accept or reject the hypothesis.

Examples of Things That Are Not Experiments

Based on the examples of experiments, you should see what is not an experiment:

• Making observations does not constitute an experiment. Initial observations often lead to an experiment, but are not a substitute for one.
• Making a model is not an experiment.
• Neither is making a poster.
• Just trying something to see what happens is not an experiment. You need a hypothesis or prediction about the outcome.
• Changing a lot of things at once isn’t an experiment. You only have one independent and one dependent variable. However, in an experiment, you might suspect the independent variable has an effect on a separate. So, you design a new experiment to test this.

Types of Experiments

There are three main types of experiments: controlled experiments, natural experiments, and field experiments,

• Controlled experiment : A controlled experiment compares two groups of samples that differ only in independent variable. For example, a drug trial compares the effect of a group taking a placebo (control group) against those getting the drug (the treatment group). Experiments in a lab or home generally are controlled experiments
• Natural experiment : Another name for a natural experiment is a quasi-experiment. In this type of experiment, the researcher does not directly control the independent variable, plus there may be other variables at play. Here, the goal is establishing a correlation between the independent and dependent variable. For example, in the formation of new elements a scientist hypothesizes that a certain collision between particles creates a new atom. But, other outcomes may be possible. Or, perhaps only decay products are observed that indicate the element, and not the new atom itself. Many fields of science rely on natural experiments, since controlled experiments aren’t always possible.
• Field experiment : While a controlled experiments takes place in a lab or other controlled setting, a field experiment occurs in a natural setting. Some phenomena cannot be readily studied in a lab or else the setting exerts an influence that affects the results. So, a field experiment may have higher validity. However, since the setting is not controlled, it is also subject to external factors and potential contamination. For example, if you study whether a certain plumage color affects bird mate selection, a field experiment in a natural environment eliminates the stressors of an artificial environment. Yet, other factors that could be controlled in a lab may influence results. For example, nutrition and health are controlled in a lab, but not in the field.
• Bailey, R.A. (2008). Design of Comparative Experiments . Cambridge: Cambridge University Press. ISBN 9780521683579.
• di Francia, G. Toraldo (1981). The Investigation of the Physical World . Cambridge University Press. ISBN 0-521-29925-X.
• Hinkelmann, Klaus; Kempthorne, Oscar (2008). Design and Analysis of Experiments. Volume I: Introduction to Experimental Design (2nd ed.). Wiley. ISBN 978-0-471-72756-9.
• Holland, Paul W. (December 1986). “Statistics and Causal Inference”.  Journal of the American Statistical Association . 81 (396): 945–960. doi: 10.2307/2289064
• Stohr-Hunt, Patricia (1996). “An Analysis of Frequency of Hands-on Experience and Science Achievement”. Journal of Research in Science Teaching . 33 (1): 101–109. doi: 10.1002/(SICI)1098-2736(199601)33:1<101::AID-TEA6>3.0.CO;2-Z

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/ɛkˈspirɪmɪnt/, /ɛkˈspɛrɪmənt/.

Other forms: experiments; experimenting; experimented

If you see your science-loving neighbor headed home with a power cord, a handful of test tubes, a stopwatch, and a bag of potatoes, there’s probably no need to be alarmed. There’s a good chance he’s only conducting an experiment , a scientific test conducted under controlled conditions.

To refer to a scientific test, use the noun experiment . If you want to describe the work done in conducting such a test, experiment will do the trick as well, since it can also act as a verb, as in "scientists experiment with helium." You can also use it more generally to describe trying a new method or idea. For example, you could experiment with a new hairstyle or different routes to get to school or work.

• noun the act of conducting a controlled test or investigation synonyms: experimentation see more see less types: show 4 types... hide 4 types... testing the act of subjecting to experimental test in order to determine how well something works trial and error experimenting until a solution is found Michelson-Morley experiment a celebrated experiment conducted by Albert Michelson and Edward Morley; their failure to detect any influence of the earth's motion on the velocity of light was the starting point for Einstein's theory of relativity control experiment an experiment designed to control for variables affecting the results of another experiment type of: research project , scientific research research into questions posed by scientific theories and hypotheses
• noun the testing of an idea “it was an experiment in living” synonyms: experimentation see more see less types: show 7 types... hide 7 types... pilot experiment a preliminary experiment whose outcome can lead to a more extensive experiment test , trial , trial run , tryout trying something to find out about it field test , field trial a test of the performance of some new product under the conditions in which it will be used alpha test (computer science) a first test of an experimental product (such as computer software) carried out by the developer beta test (computer science) a second test of an experimental product (such as computer software) carried out by an outside organization road test a test to insure that a vehicle is roadworthy trial balloon a test of public opinion type of: enquiry , inquiry , research a search for knowledge
• noun a venture at something new or different “as an experiment he decided to grow a beard” see more see less type of: venture any venturesome undertaking especially one with an uncertain outcome
• verb conduct a test or investigation “We are experimenting with the new drug in order to fight this disease” synonyms: try out try something new, as in order to gain experience see more see less type of: investigate , look into investigate scientifically
• verb try something new, as in order to gain experience “The composer experimented with a new style” synonyms: try out

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Scientific Method Vocabulary Terms

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Scientific experiments involve variables , controls, hypotheses , and a host of other concepts and terms that might be confusing.

Glossary of Science Terms

Here is a glossary of important science experiment terms and definitions:

• Central Limit Theorem: States that with a large enough sample, the sample mean will be normally distributed. A normally distributed sample mean is necessary to apply the t- test, so if you are planning to perform a statistical analysis of experimental data, it's important to have a sufficiently large sample.
• Conclusion: Determination of whether the hypothesis should be accepted or rejected.
• Control Group: Test subjects randomly assigned to not receive the experimental treatment.
• Control Variable: Any variable that does not change during an experiment. Also known as a constant variable.
• Data   (singular: datum) : Facts, numbers, or values obtained in an experiment.
• Dependent Variable: The variable that responds to the independent variable. The dependent variable is the one being measured in the experiment. Also known as the dependent measure or responding variable.
• Double-Blind : When neither the researcher nor the subject knows whether the subject is receiving the treatment or a placebo. "Blinding" helps reduce biased results.
• Empty Control Group: A type of control group that does not receive any treatment, including a placebo.
• Experimental Group: Test subjects randomly assigned to receive the experimental treatment.
• Extraneous Variable: Extra variables (not independent, dependent, or control variables) that might influence an experiment but are not accounted for or measured or are beyond control. Examples might include factors you consider unimportant at the time of an experiment, such as the manufacturer of the glassware in a reaction or the color of paper used to make a paper airplane.
• Hypothesis: A prediction of whether the independent variable will have an effect on the dependent variable or a prediction of the nature of the effect. 
• Independence  or  Independently:  When one factor does not exert influence on another. For example, what one study participant does should not influence what another participant does. They make decisions independently. Independence is critical for a meaningful statistical analysis.
• Independent Random Assignment: Randomly selecting whether a test subject will be in a treatment or control group.
• Independent Variable : The variable that is manipulated or changed by the researcher.
• Independent Variable Levels: Changing the independent variable from one value to another (e.g., different drug doses, different amounts of time). The different values are called "levels."
• Inferential Statistics: Statistics (math) applied to infer characteristics of a population-based on a representative sample from the population.
• Internal Validity: When an experiment can accurately determine whether the independent variable produces an effect.
• Mean: The average calculated by adding all the scores and then dividing by the number of scores.
• Null Hypothesis : The "no difference" or "no effect" hypothesis, which predicts the treatment will not have an effect on the subject. The null hypothesis is useful because it is easier to assess with a statistical analysis than other forms of a hypothesis.
• Null Results (Nonsignificant Results): Results that do not disprove the null hypothesis. Null results don't prove the null hypothesis because the results may have resulted from a lack of power. Some null results are type 2 errors.
• p < 0.05: An indication of how often chance alone could account for the effect of the experimental treatment. A value p < 0.05 means that five times out of a hundred, you could expect this difference between the two groups purely by chance. Since the possibility of the effect occurring by chance is so small, the researcher may conclude the experimental treatment did indeed have an effect. Other p, or probability, values are possible. The 0.05 or 5% limit simply is a common benchmark of statistical significance.
• Placebo (Placebo Treatment):  A fake treatment that should have no effect outside the power of suggestion. Example: In drug trials, test patients may be given a pill containing the drug or a placebo, which resembles the drug (pill, injection, liquid) but doesn't contain the active ingredient.
• Population: The entire group the researcher is studying. If the researcher cannot gather data from the population, studying large random samples taken from the population can be used to estimate how the population would respond.
• Power: The ability to observe differences or avoid making Type 2 errors.
• Random or Randomness : Selected or performed without following any pattern or method. To avoid unintentional bias, researchers often use random number generators or flip coins to make selections.
• Results: The explanation or interpretation of experimental data.
• Simple Experiment : A basic experiment designed to assess whether there is a cause and effect relationship or to test a prediction. A fundamental simple experiment might have only one test subject, compared with a controlled experiment , which has at least two groups.
• Single-Blind: When either the experimenter or subject is unaware whether the subject is getting the treatment or a placebo. Blinding the researcher helps prevent bias when the results are analyzed. Blinding the subject prevents the participant from having a biased reaction.
• Statistical Significance: Observation, based on the application of a statistical test, that a relationship probably is not due to pure chance. The probability is stated (e.g., p < 0.05) and the results are said to be statistically significant.
• T-Test: Common statistical data analysis applied to experimental data to test a hypothesis. The t -test computes the ratio between the difference between the group means and the standard error of the difference, a measure of the likelihood the group means could differ purely by chance. A rule of thumb is that the results are statistically significant if you observe a difference between the values that is three times larger than the standard error of the difference, but it's best to look up the ratio required for significance on a t-table .
• Type I Error (Type 1 Error): Occurs when you reject the null hypothesis, but it was actually true. If you perform the t -test and set p < 0.05, there is less than a 5% chance you could make a Type I error by rejecting the hypothesis based on random fluctuations in the data.
• Type II Error (Type 2 Error): Occurs when you accept the null hypothesis, but it was actually false. The experimental conditions had an effect, but the researcher failed to find it statistically significant.
• Null Hypothesis Examples
• Difference Between Independent and Dependent Variables
• Examples of Independent and Dependent Variables
• What Is a Double Blind Experiment?
• What Is a Hypothesis? (Science)
• The Difference Between Type I and Type II Errors in Hypothesis Testing
• Example of a Permutation Test
• Understanding Simple vs Controlled Experiments
• Six Steps of the Scientific Method
• The Difference Between Control Group and Experimental Group
• Null Hypothesis Definition and Examples
• What Is the Difference Between Alpha and P-Values?
• What Are the Elements of a Good Hypothesis?
• What Is an Experiment? Definition and Design
• What Is a P-Value?
• What Level of Alpha Determines Statistical Significance?

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experimental

Definition of experimental

• developmental

Examples of experimental in a Sentence

These examples are programmatically compiled from various online sources to illustrate current usage of the word 'experimental.' Any opinions expressed in the examples do not represent those of Merriam-Webster or its editors. Send us feedback about these examples.

Word History

Middle English, borrowed from Medieval Latin experīmentālis, from Latin experīmentum "testing, experience, proof" + -ālis -al entry 1 — more at experiment entry 1

15th century, in the meaning defined at sense 1

Phrases Containing experimental

• pre - experimental

Articles Related to experimental

This is the Difference Between a...

This is the Difference Between a Hypothesis and a Theory

In scientific reasoning, they're two completely different things

Dictionary Entries Near experimental

experimental design

Cite this Entry

“Experimental.” Merriam-Webster.com Dictionary , Merriam-Webster, https://www.merriam-webster.com/dictionary/experimental. Accessed 25 Jun. 2024.

Kids Definition

Kids definition of experimental, medical definition, medical definition of experimental, more from merriam-webster on experimental.

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Sentence examples for experiment from inspiring English sources

To conduct an experiment.

The word "experiment" is correct and can be used in written English. You can use it whenever you are referring to a scientific test or examination. For example, "The scientist conducted an experiment to determine the effects of the drug.".

We've started with a design and experience that is clean and simple and which allows us to experiment in real-time.

Someday, perhaps, we'll be in the mood to experiment again.

The commission found for the mass experiment in postal voting in June, though administration will need to improve.

Kansas is also $280m short on due payments for this fiscal year, following an experiment with historic tax cuts now in its fourth year.

A proposed experiment to test a way to deliver particles into the upper atmosphere using a balloon and a one kilometre-long pipe was cancelled in 2012 after it was reported that two of the scientists involved had submitted patent applications that were similar to the techniques being proposed.

It now appears that it began earlier still, as an experiment in both architecture and psychiatry, in the gardens of the hospital at Sant Boi.

The first major title to use the board was the fighting game Tekken, which originated as a test program to experiment with texture-mapped polygonal characters.

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Definition of experiment noun from the Oxford Advanced American Dictionary

• formulate/advance a theory/hypothesis
• build/construct/create/develop a simple/theoretical/mathematical model
• develop/establish/provide/use a theoretical/conceptual framework/an algorithm
• advance/argue/develop the thesis that…
• explore an idea/a concept/a hypothesis
• make a prediction/an inference
• base a prediction/your calculations on something
• investigate/evaluate/accept/challenge/reject a theory/hypothesis/model
• design an experiment/a questionnaire/a study/a test
• do research/an experiment/an analysis
• make observations/calculations
• take/record measurements
• carry out/conduct/perform an experiment/a test/a longitudinal study/observations/clinical trials
• run an experiment/a simulation/clinical trials
• repeat an experiment/a test/an analysis
• replicate a study/the results/the findings
• observe/study/examine/investigate/assess a pattern/a process/a behavior
• fund/support the research/project/study
• seek/provide/get/secure funding for research
• collect/gather/extract data/information
• yield data/evidence/similar findings/the same results
• analyze/examine the data/soil samples/a specimen
• consider/compare/interpret the results/findings
• fit the data/model
• confirm/support/verify a prediction/a hypothesis/the results/the findings
• prove a conjecture/hypothesis/theorem
• draw/make/reach the same conclusions
• read/review the records/literature
• describe/report an experiment/a study
• present/publish/summarize the results/findings
• present/publish/read/review/cite a paper in a scientific journal

Questions about grammar and vocabulary?

Find the answers with Practical English Usage online, your indispensable guide to problems in English.

• 2 a new activity, idea, or method that you try out to see what happens or what effect it has I've never cooked this before so it's an experiment. The system was installed four years ago as an experiment. experiment in something the country's brief experiment in democracy

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CERN experiment helps narrow the hunt for dark matter

• Astronomers have long observed that galaxies rotate faster than expected, suggesting the presence of an unseen substance called dark matter. 
• Despite extensive efforts, no direct evidence of dark matter has been found, prompting CERN scientists to use the NA64 facility to search for lighter forms of dark matter using high-energy muons. 
• The initial results have ruled out some dark matter scenarios, and future improvements in the experiment may enhance the chances of detecting this elusive substance.

Over the past half-century, astronomers have faced an embarrassing problem: Galaxies rotate too fast. When astronomers measure the speed of stars on the outskirts of galaxies, they are much higher than expected. It’s as if a cloud of invisible matter surrounds nearly every galaxy in the Universe. This matter interacts gravitationally and neither absorbs nor emits light. Astronomers even have a name for this ghostly substance: dark matter. 

The problem is that, despite decades of efforts, no direct evidence of dark matter has been observed. Scientists working at the CERN laboratory in Europe have created a facility that will provide new capabilities in the search for this elusive substance. They recently released their first results.

Using the CERN NA64 facility, scientists employed a high-energy beam of muons to search for a form of dark matter that has been overlooked by previous searches. This effort follows in the footsteps of a long history of experiments searching for dark matter with specific properties.

While the evidence of the rapidly spinning galaxies is very strong evidence that dark matter exists, its properties are unknown, with the possible mass of individual dark matter particles spanning an enormous range. On the light side, one theory proposes that individual particles have a mass much lower than an electron. On the heavy side, individual dark matter particles could be 30 times the mass of the Sun. 

Since the 1990s, various experiments have ruled out some possibilities; for example, most scientists now rule out very heavy dark matter, preferring models in which individual dark matter particles are atomic or smaller in size. In the early 2000s, the scientific community favored models in which dark matter particles were in the range of the mass of a proton to as much as a few thousand times heavier than that. However, with the 2010 start of operations of the Large Hadron Collider , the world’s most powerful particle accelerator, dark matter of this form is becoming increasingly disfavored. 

The NA64 facility was designed to look for possible lighter forms of dark matter. Rather than attempting to detect it directly, the NA64 experiment relies on the fact that dark matter doesn’t interact with ordinary matter as a way to detect it.

Energy conservation is a central principle of physics. It says that energy can neither be created nor destroyed. If you measure the energy of a system at one time, it will remain the same, no matter what happens. It’s like a bank account that doesn’t pay interest. Whatever you deposit, you can take out. If the two numbers don’t balance, somebody stole some of your money. 

The basic principle of the NA64 experiment is similar. High-energy muons crash into a target, interacting with atomic nuclei. After the collision, the energy of the debris is measured. If the energy after the collision is less than the energy before the collision, then the energy has somehow escaped, undetected. One possibility is that a dark matter particle was created. Because dark matter doesn’t interact, it would have traveled through the detector without interacting. Essentially, you know it’s there because you didn’t see it.

The NA64 experiment looked for dark matter in the range of about 0.5% to 50% of the mass of a proton. Besides being a range of masses that had not been fully explored using a muon beam, this range was fortuitous for other reasons as well.

Muons are essentially heavy electrons. They have the same electric charge and spin characteristics as electrons, but muons are heavier. Having both electric charge and spin means that muons act like tiny magnets and the magnetic properties of muons have been mysterious for the past couple of decades. The name given to this magnetic property is “muon g-2,” and scientists have both predicted and measured muon g-2 very precisely. They agree, digit for digit, for seven digits, and then disagree in the eighth. The measurement was made by the Muon g-2 collaboration , and the prediction was made by the Muon g-2 Theory Initiative .

Having data and prediction disagree is not inherently surprising. After all, measurement and theoretical prediction rarely agree exactly. However, if the theory is correct and the measurement is accurate, the two should be close and should agree within the stated uncertainties.

Future experiments

The most recent measurement and prediction do not agree with the stated uncertainties, and this has set off a firestorm of discussion in the scientific community. When very precise predictions and measurements disagree, it is often a sign of an impending discovery. Thus, any measurement of muons could help resolve the situation.

The NA64 collaboration studied 20 billion muon collisions, looking for collisions with the right amount of missing energy. None were observed. This result has both ruled out a range of dark matter scenarios, as well as ruled out certain explanations for the muon g-2 mystery.

The NA64 experiment is still being developed and future improvements are expected to create a thousandfold increase in the number of muons to be studied. In tandem with the increased beam, improved equipment will result in a tenfold reduction in measurement uncertainties associated with mismeasuring muon energy. When these two improvements are achieved, the resulting apparatus will significantly improve the experiment’s capabilities and it is possible that future measurements could find the elusive dark matter.

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Definition of experiment – Learner’s Dictionary

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• scientific experiments
• inhumane experiments on monkeys
• The table below shows the results of the experiment.
• Parallel experiments are being conducted in both countries .
• There is a growing debate on medical experiments.

experiment verb [I] ( TRY SOMETHING )

Experiment verb [i] ( do tests ).

• experimentation

(Definition of experiment from the Cambridge Learner's Dictionary © Cambridge University Press)

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make ends meet

to have just enough money to pay for the things that you need

Fakes and forgeries (Things that are not what they seem to be)

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National Academies Issue New Broad Definition of Long COVID

Miriam E. Tucker

June 11, 2024

A new broadly inclusive definition of long COVID from the National Academies of Sciences, Engineering, and Medicine (NASEM) has been developed with the aim of improving consistency, documentation, and treatment for both adults and children.

According to the 2024 NASEM definition of long COVID issued on June 11, 2024, "Long COVID is an infection-associated chronic condition that occurs after SARS-CoV-2 infection and is present for at least 3 months as a continuous, relapsing and remitting, or progressive disease state that affects one or more organ systems." 

People with long COVID may present with one or more of a long list of symptoms, such as shortness of breath, rapid heartbeat, extreme fatigue, post-exertional malaise, or sleep disturbance and with single or multiple diagnosable conditions, including interstitial lung disease, arrhythmias, postural orthostatic tachycardia syndrome (POTS), myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS), diabetes, or autoimmune disorders. The condition can exacerbate preexisting health conditions or present as new ones. 

The definition does not require laboratory confirmation or other proof of initial infection. Long COVID can follow SARS-CoV-2 infection of any severity, including asymptomatic infections, whether or not they were initially recognized. 

Several working definitions and terms for long COVID had previously been proposed, including those from the World Health Organization (WHO) and the US Centers for Disease Control and Prevention, but no common definition or terminology had been established.

The new definition was developed at the request of the Administration for Strategic Preparedness and Response and the Office of the Assistant Secretary for Health (OASH). It was written by a multistakeholder panel convened by NASEM, which recommended that the new definition be universally adopted by the federal government, clinical societies and associations, public health practitioners, clinicians, payers, the drug industry, and others using the term long COVID. 

Recent surveys suggest that approximately 7% of Americans have experienced or are experiencing long COVID. "It's millions of people," panel chair Harvey V. Fineberg, MD, president of the Gordon and Betty Moore Foundation, told Medscape Medical News . 

The new definition "does not erase the problem of clinical judgment…But we think this definition has the real advantage of elevating to the clinician's mind the real likelihood in the current environment of prevalence of this virus that a presenting patient's strange symptoms are both real and maybe related as an expression of long COVID," Fineberg noted. 

One way this new definition differs from previous ones such as WHO's, he said, is "they talk about a diagnosis of exclusion. One of the important points in our definition is that other diagnosable conditions like ME/CFS or POTS can be part of the picture of long COVID. They are not alternative. They are, in fact, an expression of long COVID."

Indeed, the NASEM report also introduces the term infection-association chronic condition (IACC). This was important, Fineberg said, "because it's the larger family of conditions of which long COVID is a part. It emphasizes a relatedness of long COVID to other conditions that can follow from a variety of infections. We also adopted the term 'disease state' to convey the seriousness and reality of this condition in the lives of patients." 

Comments on New Definition

In a statement provided to Medscape Medical News , Lucinda Bateman, MD, and Brayden Yellman, MD, co-medical directors of the Bateman-Horne Center in Salt Lake City, said that "describing long COVID as an IACC…not only meets the NASEM goal of allowing clinicians, researchers, and public health officials to meaningfully identify and serve all persons who suffer illness or disability in the wake of a SARS-CoV-2 infection, but also draws direct comparison to other known IACC's (such as ME/CFS, post-treatment Lyme, POTS) that have been plaguing many for decades."

Fineberg noted another important aspect of the NASEM report: "Our definition includes an explicit statement on equity, explaining that long COVID can affect anyone, young and old, different races, different ages, different sexes, different genders, different orientations, different socioeconomic conditions…This does not mean that every single person is at equal risk. There are risk factors, but the important point is the universal nature of this as a condition."

Two clinical directors of long COVID programs who were contacted by Medscape Medical News praised the new definition. Zijian Chen, MD, director of Mount Sinai's Center for Post-COVID Care, New York, said that it's "very similar to the definition that we have used for our clinical practice since 2020. It is very important that the broad definition helps to be inclusive of all patients that may be affected. The inclusion of children as a consideration is important as well, since there is routinely less focus on children because they tend to have less disease frequency…The creation of a unified definition helps both with clinical practice and research."

Nisha Viswanathan, MD, director of the long COVID program at the University of California, Los Angeles, said: "I think they left it intentionally broad for the medical practitioner to not necessarily use the definition to rule out individuals, but to perhaps use more of a clinical gestalt to help rule in this diagnosis…I think this definition is providing clarity to healthcare providers on what exactly would be falling under the long-COVID diagnosis header." 

Viswanathan also said that she anticipates this definition to help patients make their case in filing disability claims. "Because long COVID has not previously had a good fleshed-out definition, it was very easy for disability providers to reject claims for patients who continue to have symptoms …I actually think this might help our patients ultimately in their attempt to be able to have the ability to care for themselves when they're disabled enough to not be able to work."

Written into the report is the expectation that the definition "will evolve as new evidence emerges and the understanding of long COVID matures." The writing committee calls for reexamination in "no more than 3 years." Factors that would prompt a reevaluation could include improved testing methods, discovery of medical factors and/or biomarkers that distinguish long COVID from other conditions, and new treatments. 

Meanwhile, Fineberg told Medscape Medical News , "If this definition adds to the readiness, awareness, openness, and response to the patient with long COVID, it will have done its job." 

Fineberg, Bateman, Yellman, Viswanathan, and Chen have no relevant disclosures . 

Miriam E. Tucker is a freelance journalist based in the Washington, DC area. She is a regular contributor to Medscape, with other work appearing in  The Washington Post , NPR's  Shots blog, and Diatribe. She is on X (formerly Twitter) @MiriamETucker. 

Send comments and news tips to [email protected] .

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Science News

Long covid finally gets a universal definition.

The new description includes more than 200 symptoms and doesn’t put limits on when they start

Long COVID affects millions of Americans of almost all ages, but there has been no standard definition for the condition until now.

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By Tina Hesman Saey

June 12, 2024 at 9:00 am

A sweeping new definition of long COVID could help affected people get recognition of their condition and improve diagnosis and treatment.

The U.S. National Academies of Sciences, Engineering and Medicine announced the definition for long COVID June 11.

Previous definitions of long COVID have been all over the map , each with its own set of accepted symptoms, timelines and requirements for proof of infection ( SN: 7/29/22 ).

That lack of standardization “left many patients in the lurch without clear ability to be recognized for the condition that they had, with difficulty explaining to family and even to their caregivers,” says Harvey Fineberg, a public health expert who chaired the committee that drafted the definition. “We heard from literally hundreds of people experiencing long COVID about the challenges that they had in being heard, in gaining access to care and obtaining the care they needed.”

More than 1,300 people contributed to the definition . The committee decided to adopt the patients’ own term “long COVID” instead of more medical terms such as “post-acute sequelae of COVID-19” that have also been used to describe the long-term condition. Adoption of the name the patients advocated for gives validation to everyone with the condition who has been struggling, sometimes for years, to have their experience acknowledged, says Daria Oller, a physical therapist in New Jersey who developed long COVID in 2020. “Now, people are trying to not use the term long COVID, and all of us, patients from the first wave, are fighting. We were ignored. That’s ours. We named it.”

The committee chose to go with the name because it’s simple, familiar and easy to communicate, Fineberg said during a webinar introducing the definition. 

No one knows exactly how many people have long COVID, but a recent survey found that more than 17 percent of adults in the United States have experienced the condition. While the National Academies don’t have regulatory or legal power to enforce adoption of the definition, the respected body of scientific experts’ recommendations are often used in making regulatory decisions, determining medical and scientific policies and crafting laws.

Here’s what to know about the long COVID definition.

What is long COVID?

It’s a medical condition that belongs to a family of chronic conditions that kick in after infections with viruses, bacteria, fungi or parasites. That includes chronic health problems such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Lyme-associated chronic illnesses.

According to the National Academies’ definition, long COVID is a medical condition that persists for at least three months after an infection with SARS-CoV-2, the coronavirus that causes COVID-19. Long COVID can affect any organ or system in the body. People may have any of more than 200 symptoms, which may include difficulty breathing, brain fog , blood clots , dizziness, extreme fatigue after exercising, loss of taste or smell, fast heart rate, diarrhea, constipation, diabetes and autoimmune diseases such as lupus ( SN: 2/2/22 ; SN: 8/21/23 ; SN: 1/4/22 ). Those symptoms can appear alone or in multiple combinations, can be continuous, get progressively worse or have bouts in which the patient gets better and then worse again.

Chronic symptoms can affect people who originally had mild to severe COVID and can even strike people who didn’t have any symptoms at all from their original infection. For that reason, the committee that crafted the Academies’ definition says that people don’t need to have had a positive COVID test to be diagnosed with long COVID.

The condition can strike adults and children and can start weeks or months after seeming recovery from the initial infection. The committee didn’t put an upper limit on how long after getting the original illness that long COVID could start.

There are no blood tests or biomarkers that doctors can use to reliably diagnose long COVID right now. The report calls for continued research to find such diagnostic tools.

This definition follows a June 5 report that the Social Security Administration asked the National Academies to prepare. That report similarly found that long COVID can have debilitating symptoms that can affect people’s physical function, quality of life and their ability to work or perform in school for years.

Why is the definition so broad?

The definition is “intentionally inclusive,” the committee says.

“We wanted to be sure that long COVID was not regarded as a diagnosis of exclusion,” says Fineberg, who is president of the Gordon and Betty Moore Foundation, based in Palo Alto, Calif. Everyone with lingering effects from a coronavirus infection should fall under the broad umbrella erected by the new definition. That means some people who have long-term health problems caused by a different infectious disease or other cause might be mistakenly diagnosed with long COVID, Fineberg admits.

That big-tent approach is essential for health equity, says committee member Monica Verduzco-Gutierrez, a physical medicine and rehabilitation physician at the University of Texas Health Science Center at San Antonio. The committee wanted to make sure that people who don’t have access to testing — because tests weren’t available early on and free testing has ended now — or who got a false negative test or had asymptomatic infections could still be included in the definition. 

“I think they got it right in the sense that they didn’t leave anybody out,” says Ziyad Al-Aly, head of research at the VA Saint Louis Health Care System. Al-Aly was one of the independent experts who reviewed the report.

Will the definition change?

Yes. The report calls for revision of the definition in no more than three years and possibly sooner if new science warrants it.

“We’re very mindful that the definition is only good as far as science can take us at this time,” Fineberg says.

What will the definition mean for the health care for people with long COVID?

Having “the gravitas of the National Academy of Medicine behind” the definition “will be seen by patients and patients advocates as legitimizing the illness which they have been complaining about,” says Al-Aly. “There’s a lot of gaslighting by physicians and by providers, and by the community [and] our society at large.”

Some people have dismissed the condition as being a mental health disorder, but plenty of research has established that there are widespread biological changes, Verduzco-Gutierrez says. The definition “makes it clear that long COVID is a physical health condition.”

Not requiring a positive test to be diagnosed with long COVID “is huge” for Oller, who has no proof that she was infected with SARS-CoV-2 in early 2020. “We couldn’t get tested. There were long lines, and you needed symptoms that I didn’t have.”

Before COVID, Oller was a runner and dancer. After, she had difficulty breathing and pains in her chest, which she now thinks may have been caused by microclots in her lungs. She’s had a battery of health problems that have persisted. Though many symptoms have improved, they haven’t all gone away, and Oller has accepted that she may be dealing some unwanted aftereffects of COVID-19 for life. Early on, she had no name for what she was experiencing and encountered much skepticism that anything was actually wrong with her, even from other medical professionals.

Oller is a founding member of long COVID Physio , an international peer group of people with long COVID and their allies. She was not involved in the National Academies’ report but welcomes the broad definition.

It will be something patients can take to their doctors to bolster their claims, Oller says. She understands some of the difficulties clinicians have with diagnosing long COVID. “It’s hard because it challenges a lot of our biases,” she says. “Exercise makes us worse, trying harder makes us worse. … It’s easier to blame the patient and be like, ‘Oh, you’re not trying. You’re lazy. You just want to get on disability. It’s in your head.’ It’s easier to just send them on that route than to read through all the literature.”

Over time, Oller says, the definition may be refined to include subtypes of long COVID, much the way cancer is an overarching definition of runaway cell growth but is divided by where the cancer occurs and the mutations that cause it. But for now, she says, starting out broad will allow people whose symptoms don’t “fit into a nice little package” to have their condition recognized and acknowledged.

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• Open access
• Published: 24 June 2024

Silencing LINC00987 ameliorates adriamycin resistance of acute myeloid leukemia via miR-4458/HMGA2 axis

• Yue Liu 1   na1 ,
• Xiao-ya Zhu 2   na1 ,
• Li-li Liao 3 ,
• Zhan-hui Zhang 3 ,
• Tao-sheng Huang 3 ,
• Ling Zhang 4 ,
• Xi-wen Jiang 3 &
• Yi Ma 1 , 5 , 6  

Biology Direct volume  19 , Article number:  49 ( 2024 ) Cite this article

Metrics details

Most patients with acute myeloid leukemia (AML) eventually develop drug resistance, leading to a poor prognosis. Dysregulated long gene non coding RNAs (lincRNAs) have been implicated in chemoresistance in AML. Unfortunately, the effects of lincRNAs which participate in regulating the Adriamycin (ADR) resistance in AML cells remain unclear. Thus, the purpose of this study is to determine LINC00987 function in ADR-resistant AML.

In this study, ADR-resistant cells were constructed. LINC00987, miRNAs, and HMGA2 mRNA expression were measured by qRT-PCR. P-GP, BCRP, and HMGA2 protein were measured by Western blot. The proliferation was analyzed by MTS and calculated IC50. Soft agar colony formation assay and TUNEL staining were used to analyze cell colony formation and apoptosis. Xenograft tumor experiment was used to analyze the xenograft tumor growth of ADR-resistant AML.

We found that higher expression of LINC00987 was observed in AML patients and associated with poor overall survival in AML patients. LINC00987 expression was increased in ADR-resistant AML cells, including ADR/MOLM13 and ADR/HL-60 cells. LINC00987 downregulation reduces ADR resistance in ADR/MOLM13 and ADR/HL-60 cells in vitro and in vivo, while LINC00987 overexpression enhanced ADR resistance in MOLM13 and HL-60 cells. Additionally, LINC00987 functions as a competing endogenous RNA for miR-4458 to affect ADR resistance in ADR/MOLM13 and ADR/HL-60 cells. HMGA2 is a target of miR-4458. LINC00987 knockdown and miR-4458 overexpression reduced HMGA2 expression. HMGA2 overexpression enhanced ADR resistance, which reversed the function of LINC00987 silencing in suppressing ADR resistance of ADR/MOLM13 and ADR/HL-60 cells.

Conclusions

Downregulation of LINC00987 weakens ADR resistance by releasing miR-4458 to deplete HMGA2 in ADR/MOLM13 and ADR/HL-60. Therefore, LINC00987 may act as the therapeutic target for treating chemoresistant AML.

Acute myeloid leukemia (AML), the most common subtype of leukemia, is the highly heterogeneous hematopoietic malignancy with a high proportion of AML in children and the elderly [ 1 ]. The main treatments for AML are chemotherapy and stem cell transplantation, which have greatly improved over the last decades [ 2 , 3 ]. Many chemotherapeutic drugs, including Adriamycin (ADR), are currently used to treat AML [ 4 , 5 ]. Unfortunately, approximately 25% of patients still suffer from multidrug resistance, leading to disease recurrence, poor chemotherapy efficacy, and a lower survival rate in AML patients [ 6 ]. Multidrug resistance was associated with the overexpression of breast cancer resistance protein (BCRP) and P-glycoprotein (P-GP) protein in cancer [ 7 ]. Compared to the untreated patients with AML, BCRP and P-GP protein were increased in relapsed patients with AML [ 8 ]. High BCRP and P-GP protein had been closely related to poor prognosis because of chemoresistance [ 9 ]. Thus, multidrug resistance is still a major obstacle for treating AML. Therefore, it is necessary to discover the molecular mechanisms of chemoresistance in AML and identify a revolutionary target to reverse chemoresistance in AML.

Dysregulation of lncRNAs (such as lncRNA CRNDE, KCNQ1OT1, and ZFAS1) is implicated in chemoresistance in AML [ 10 , 11 , 12 , 13 ]. Long intergenic non coding RNAs (lincRNAs), a type of lncRNA, are emerging as key regulators in cancer development. LincRNA can serve as a prognostic marker for AML [ 14 ]. LincRNAs can enhance the expression and biological functions of miRNA targets by acting as competitive endogenous RNAs (ceRNAs) to miRNA sponges. LINC00675 promotes the AML malignancy via sponging miR-6809 to positively regulate CDK6 expression [ 15 ]. LINC00599 attenuates AML malignancy by sponging miR-135a-5p [ 16 ]. More importantly, lincRNA is closely related to tumor resistance. LINC02321 promotes cisplatin resistance in bladder cancer [ 17 ]. LINC-PINT reduced the cisplatin chemoresistance of laryngeal carcinoma cell via sponging miR-425-5p to positively regulate PTCH1 and SHH protein [ 18 ]. In addition, LINC00239 overexpression promoted chemoresistance against doxorubicin in AML cells [ 19 ]. Unfortunately, the role and mechanism of lincRNAs in ADR-resistant AML is still not complete understood.

In the present study, lincRNAs associated with poor prognosis of leukemia were analyzed using the GEPIA website. Then, ADM-resistant acute leukemia cells were established, and lincRNA expression in AML and corresponding ADM-resistant AML cell lines was measured. LINC00987 expression was higher in ADM-resistant AML cells, then the effect of LINC00987 on ADM-resistant in AML cell lines was studied. Then, the miRNAs sponged by LINC00987 and their target genes were analyzed. Furthermore, the mechanism underlying LINC00987/miRNA/target gene-regulated ADR resistance was explored. This study aimed to identify a novel treatment target for attenuating ADR resistance in AML cell lines.

Materials and methods

Adr-resistant aml cell.

MOLM13 and HL-60 were purchased from Zqxzbio (Shanghai, China) and cultured in complete media ZQ-905 and ZQ-218 (Zqxzbio). ADR-resistant cells were induced by a low-concentration gradient increase. Briefly, the sensitivity of MOLM13 and HL-60 to ADR was detected. MOLM13 first incubated with 0.01 µmol/L ADR for two week, then Incubated with 0.02, 0.04, 0.08 µmol/L ADR for one week. When using 0.16 µmol/L incubation, MOLM13 cells showed significant death. Hence, 0.08, 0.12, and 0.16 µmol/L ADR were further used to treat for 2 weeks. When using 0.20 µmol/L ADR incubation, a large number of MOLM13 cells were dead. And the experiment did not progress after continuous cultivation for 3 times. Hence, 0.16 µmol/L ADR was used to maintain cultivation for 4 weeks for subsequent experiments. Similarly, when using 0.28 µmol/L ADR incubation, a large number of HL-60 cells were dead. And the experiment did not progress after continuous cultivation for 3 times. Hence, 0.24 µmol/L ADR was used to maintain cultivation for 4 weeks for subsequent experiments. ADR-resistant cells were constructed, and the IC50 was calculated.

Proliferation

For proliferation measurements, 1 × 10 4 transfected cells were seeded in 96-well plates for culturing. Then 10 µl AQueous One Solution reagent (Promega) was added at 0, 24, 48, and 72 h. The optical density at 490 nm (OD490 nm) was measured after cultivation for 4 h. Cell viability was calculated using the following formula: (OD 490 nm in experiment group/OD 490 nm in control group × 100%). The OD 490 was measured after different concentrations of ADR treatment at 0, 24, 48, and 72 h to calculate IC50. The assays were performed in duplicate.

Transfection

LINC00987 (NR_036466) and high mobility group AT-hook 2 (HMGA2, NM_003483) cloned into the pcDNA3.1 vector to establish the LINC00987 and HMGA2 overexpression vectors (pcDNA-LINC00987 and pcDNA-HMGA2, GENERAL bio, Guangzhou, China). Empty pcDNA3.1 vector (pcDNA-Empty) was used as a negative control. Small interfering RNAs (siRNAs) against LINC00987 (si-LINC00987), and a scramble negative control (si-NC), were chemically synthesized by Ribobio (Guangzhou, China). The miR-4458 inhibitor and negative inhibitor control (miR-NC inhibitor) were purchased from Ribobio. All transfections were performed by electroporation using an Entranster™-E (Engreen, Beijing, China). To elucidate the impact of LINC00987 on ADM-resistance, pcDNA-LINC00987 and pcDNA-Empty were transfected into MOLM13 and HL-60 cells, and si-LINC00987 and si-NC were transfected into ADR/MOLM13 and ADR/HL-60. To elucidate the relationship between LINC00987, miR-4458, and HMGA2, si-LINC00987 and miR-4458 inhibitor (or miR-NC inhibitor) or si-LINC00987 and pcDNA-HMGA2 (or pcDNA-Empty) were co-transfected into the ADR/MOLM13 and ADR/HL-60.

For RNA extraction, ADR/MOLM13, ADR/HL-60, MOLM13, and HL-60 cells were collected and isolate total RNA using TRIzol reagent (Invitrogen). Reverse transcription was carried out using the EasyScript First-Strand cDNA Synthesis SuperMix kit (TransGen Biotech, Beijing, China). The qPCR was prepared using SYBR Green qPCR SuperMix (YEASEN, Shanghai, China), according to manufacturer instructions, which was performed using the ABI PRISM® 7500 Sequence Detection System (Applied Biosystems, Foster City, CA, USA). β-actin and U6 were analyzed as internal control genes for lincRNAs and miRNAs, respectively. The primers (5′–3′) are shown in Supplementary Table 1 . The assays were performed in triplicate.

Soft agar colony formation assay

First, 1.2% and 0.7% agarose solutions were prepared. Then, 1.2% agarose solution and 2 × complete medium were mixed and added to 96-well culture plates as the base agar layer. Next, 0.7% agarose solutions and 2 × complete medium were mixed, and ADR/MOLM13, ADR/HL-60 cells, MOLM13, and HL-60 cells were suspended in complete medium and mixed with 0.7% agar. Then, 1 × 10 4 cells/well were seeded into 96-well culture plates and solidified on the base agar layer. The 96-well culture plates were incubated at 37 °C in a 5% CO 2 atmosphere for 7 days. Complete medium (200 µL was added every two days during the incubation period. After culturing for 7 days, the number of cell clones was counted by imaging at 100x magnification using a LEICA microscope. The assays were performed in triplicate.

TUNEL staining

TUNEL staining was used to detect cell apoptosis. Briefly, the cell slice was incubated at 37 °C for 30 min and washed by PBS. The DeadEnd™ Fluorometric TUNEL System (G3250, Promega) was added to the slice, which was incubated to 1 h in 37 °C and dark condition. Then the slice was washed with PBS and dried for mounting. TUNEL staining was observed using a digital pathological section (fluorescence) scanning analyzer. The assays were performed in triplicate.

Western blot

Total protein (30 µg per lane) was isolated using RIPA buffer. After 12% and 8% SDS-PAGE, the proteins were transferred onto PVDF membranes. Membranes were blocked, incubated with primary antibodies, The primary antibodies used were as follows: rabbit monoclonal anti-P glycoprotein (P-GP; 1:1000, ab170904, Abcam, San Diego, CA, USA), breast cancer resistance protein (BCRP, 1:1000, ab207732, Abcam), HMGA2 (1:1000, ab246513, Abcam), and anti-GAPDH (1:10000, AF2071, Affinity, San Diego, CA, USA). Horseradish peroxidase-conjugated secondary goat anti-mouse IgG (G-21,040, Ebioscience, 1:1000) was incubated at 1 h in 25 °C. Protein abundance was shown by enhanced chemiluminescent reagent (Thermo Scientific Pierce, Rockford, IL, USA).

Xenograft tumor

A total of 20 Female 5-week-old BALB/c nude mice (13–15 g) were from the Guangdong Medical Laboratory Animal Center (SCXK(Yue)2018-0002, Guangzhou, China) and were fed with autoclaved standard laboratory feed and given free access to sterile drinking water under SPF conditions (25 ℃ and 12-h light/dark cycle). Lentiviruses carrying sh1-LINC00987 and empty lentiviruses (Laideliankang, Guangzhou, China) were infected into the ADR/MOLM13 and ADR/HL-60 cells. To screen cells infected with lentivirus, ADR/MOLM13 and ADR/HL-60 cells were cultured in a complete culture medium containing 4 µg/ml puromycin at 48 h after infection, and then the medium was changed every 2 days. Simultaneously, ADR/MOLM13 and ADR/HL-60 cells which had not infected with lentivirus were used as control experiments. After all ADR/MOLM13 and ADR/HL-60 cells in the control experiments were dead, ADR/MOLM13 and ADR/HL-60 cells which infected with lentivirus were cultured in a complete culture medium with 1 µg/ml puromycin. The stable cell lines were obtained after continued to pass on for 3 generations. Then the stable cells were collected and made into single cell suspension at a density of 5 × 10 6 cells/mL, 100 µL of which was inoculated subcutaneously into the dorsal root of the right hind limb of nude mice. Nude mice were randomization divided into four groups ( n  = 5): ADR/MOLM13-sh-NC, ADR/MOLM13 + sh1-LINC00987, ADR/HL-60-sh-NC, and ADR/HL-60 + sh1-LINC00987. ADR solution (10 mg/kg) was intravenously administered every 5 days. The mice were euthanized at 30 day after inoculation, and the subcutaneous tumor was removed. The length and width of the subcutaneous tumor was measured by the digital caliper (Guanglu, Guilin, China), and the volume of subcutaneous tumor was calculated: volume = (length × width × width)/2. The animal experiments were approved by the GIBH Application to Use Animals for Research (A5748-01) in accordance with the Basel Declaration.

Luciferase reporter and Ago2-RIP assays

The psi-CHECK2 luciferase reporter gene vectors which cloned the wild-type LINC00987 (WT LINC00987), wild-type HMGA2 mRNA 3′-UTR (WT HMGA2), mutant LINC00987 (MUT LINC00987; All sites that bind to miR-4458 have undergone mutations), mutant HMGA2 mRNA 3′-UTR (MUT HMGA2; All sites that bind to miR-4458 have undergone mutations) (GENERAL bio, Guangzhou, China) were transfected with into ADR/MOLM13 and ADR/HL-60 cells. And miR-4458 mimic or NC mimic was co-transfected with into ADR/MOLM13 and ADR/HL-60 cells. After 48 h, Renilla (R) and firefly (F) luciferase activity were was monitored using the Dual-Luciferase Assay kit (Promega) and calculated R/F. AGO2-RIP assay was performed using EZ-Magna RIP RNA-Binding Protein Immunoprecipitation Kit (Merck Millipore, Bedford, MA, USA) following the manufacturer’s instructions. Magnetic beads were conjugated with human anti-Ago2 antibody or anti-IgG antibody (negative control). In addition, LINC00987and miR-4458 expression was measured by qRT-PCR.

Bioinformatics analysis

To analyze the role of lincRNA in prognosis judgment and drug resistance, the top 100 differentially survival genes were analyzed in “Most Differential Survival Genes” module using the ‘Survival Analysis’ of GEPIA ( http://gepia2.cancer-pku.cn/#general ). In addition, the relationship between LINC00987, LINC00152, and LINC00982 expression with LAML survival were analyzed in “Survival Plots” module using the ‘Survival Analysis’ of using GEPIA. And LINC00987, LINC00152, and LINC00982 expression in LAML patients were analyzed in “Box Plots” module using the ‘Expression DIY’ of GEPIA. The top 100 genes that had a similar expression trend to LINC00987 in AML were analyzed using the ‘Similar Genes Detection’ of using GEPIA. Next, miRcord ( http://www.mircode.org/index.php ) and LncBase Predicted v2 ( https://dianalab.e-ce.uth.gr/html/diana/web/index.php?r=lncbasev2%2Findex-predicted ) were used to analyze the potential miRNA sponges of LINC00987. Finally, Starbase 3.0 ( https://rnasysu.com/encori/index.php ), miRBD ( https://mirdb.org/ ), and Targetscan 8.0 ( https://www.targetscan.org/vert_80/ ) were used to analyze the potential targets of miR-4458. The clinical correlation of LINC00987 vs. miR-4458 or HMGA2 v miR-4458 in AML patients were analyzed by Starbase 3.0 ( https://rnasysu.com/encori/index.php ).

Statistical analysis

All data in the bar graph are presented as mean ± standard deviation. One-way analysis of variance (ANOVA) followed by Turney’s test was used to analyze statistical differences between more than 2 groups using SPSS software (version 19.0; SPSS Inc., Chicago, IL, USA).

LINC00987 expression was upregulated in ADR-resistant AML cells

To analyze the role of lincRNA in prognosis judgment and drug resistance, the top 100 differentially survival genes were analyzed using GEPIA. Then it found that three lincRNAs (LINC00987, LINC00152, and LINC00982) were associated with poor overall survival in AML patients (Fig.  1 A). Higher expression of LINC00987 and LINC00982 was observed in AML patients than in normal individuals, while lower LINC00152 expression was observed (Fig.  1 B). To detect LINC00987, LINC00152, and LINC00982 expression in ADR-resistant AML cells, ADR/MOLM13 and ADR/HL-60 cells were constructed. More interestingly, compared to the corresponding AML cells (MOLM13 and HL-60), the IC50 of the drug-resistant AML cell lines (ADR/MOLM13 and ADR/HL-60) was significantly increased (Supplementary Fig.  1 ). The results showed that the ADR-resistant AML cells were successfully constructed. Additionally, LINC00987 and LINC00982 expression was significantly increased in ADR/MOLM13 and ADR/HL-60 cells compared with that in MOLM13 and HL-60 cells, especially the expression of LINC00987 (Fig.  1 C). ADR treatment reduced the expression of LINC00987 in HL-60 and MOLM13 cell (Supplementary Fig.  2 ). Thus, LINC00987 was chosen to study its effect on drug resistance in AML cells.

LINC00987 expression was higher in AML patients and associated with poor overall survival. ( A ) The relationship between LINC00987, LINC00152, and LINC00982 expression with LAML survival were analyzed using GEPIA. ( B ) LINC00987, LINC00152, and LINC00982 expression in LAML patients were analyzed via GEPIA. ( C ) LINC00987, LINC00152, and LINC00982 expression in MOLM13, HL-60, ADR/MOLM13, and ADR/HL-60 cells were measured via RT-qPCR. *** P  < 0.001

LINC00987 downregulation reduces the ADR resistance of ADR-resistant AML cells

To detect the effect of LINC00987 on ADR-resistant AML cells, ADR/MOLM13 and ADR/HL-60 cells were transfected with LINC00987 siRNA and then treated with 0.2 µM (≈ IC 50 of MOLM13) ADR. LINC00987 expression in ADR/MOLM13 and ADR/HL-60 cells was significantly inhibited after transfection with siRNAs, especially si1-LINC00987 (Fig.  2 A). Under 0.2 µM ADR treatment, the survival rate and the number of cell clone formation of ADR/MOLM13 and ADR/HL-60 cells in the si1-LINC00987 group was significantly lower than that in the si-NC group (Fig.  2 B and C). In addition, compared to the sh-NC group, LINC00987 expression in xenograft tumor was were significantly decreased in sh1-LINC00987 group and the tumor volume were significantly decreased in sh1-LINC00987 group under 50 µM ADR treatment (Fig.  2 D). The IC50 of si1-LINC00987-transfected ADR/MOLM13 (0.16 µmol/L) and ADR/HL-60 (0.29 µmol/L) cells were evidently reduced compared to the IC50 of si1-NC-transfected (2.08 µmol/L) and ADR/HL-60 (8.29 µmol/L) cells (Fig.  3 A). The expression of the drug resistance proteins (P-GP and BCRP) in the si1-LINC00987 group was clearly lower than that in the si-NC group (Fig.  3 B). More interestingly, under 0.2 µM ADR treatment, the apoptosis of ADR/MOLM13 and ADR/HL-60 cells in the si1-LINC00987 group was noticeably higher than that in si-NC group (Fig.  3 C).

Decreased expression of LINC00987 reduces the cell viability and ADR-resistance of AML cells. ( A ) LINC00987 expression in ADR/MOLM13 and ADR/HL-60 cells was measured via RT-qPCR after siRNA transfection at 24 h. ( B ) The proliferation of ADR/MOLM13 and ADR/HL-60 cells was detected by CCK8 after siRNA transfection at 24 h under 0.2 µM ADR treatment. The cell viability was calculated according to proliferation. ( C ) Clone formation of ADR/MOLM13 and ADR/HL-60 cells was detected by soft agar colony formation assay. The number of cell clone formations was counted by imaging at 100x magnification. (D) Xenograft tumor was used to analyze the effect of LINC00987-silenced on the size of tumor growth. And LINC00987 expression in Xenograft tumor was measured via RT-qPCR. * P  < 0.005 and *** P  < 0.001

LINC00987 downexpression reduces the ADR resistance of ADR-resistant AML cells under 0.2 µM ADR treatment. ( A ) The IC50 of ADR for si1-LINC00987-transfected ADR/MOLM13 and ADR/HL-60 cells were shown after different concentrations of ADR treatment at 24 h. ( B ) Under 0.2 µM ADR treatment, P-GP and BCRP expression in ADR/MOLM13 and ADR/HL-60 cells were measured by western blotting. ( C ) Apoptosis of ADR/MOLM13 and ADR/HL-60 cells were detected by TUNEL staining and imaging at 400× magnification. *** P  < 0.001

LINC00987 overexpression enhances the ADR-resistance of AML cells

To detect the effect of LINC00987 on ADR resistance in AML cells, MOLM13 and HL-60 cells which were transfected into pcDNA-LINC00987 and then treated with 0.2 µM ADR. LINC00987 expression in MOLM13 and HL-60 cells was significantly higher in the pcDNA-LINC00987 group than that in the pcDNA-empty group (Fig.  4 A). Under 0.2 µmol/L ADR treatment, the cell viability and the number of cell clone formations of MOLM13 and HL-60 cells in pcDNA-LINC00987 group was significantly higher than that in pcDNA-Empty group (Fig.  4 B and C). The IC50 of pcDNA-LINC00987-treanfected MOLM13 (3.19 µmol/L) and HL-60 (6.25 µmol/L) cells were evidently increased compared with the IC50 of MOLM13 (0.25 µmol/L, ) and HL-60 (0.30 µmol/L) cells (Fig.  4 D). In addition, P-GP and BCRP expression in the pcDNA-LINC00987 group was visibly higher than that in the pcDNA-empty group (Fig.  4 E). More interestingly, under 0.2 µM ADR treatment, the apoptosis of MOLM13 and HL-60 cells in the pcDNA-LINC00987 group was noticeably lower than that in pcDNA-Empty group (Fig.  4 F).

LINC00987 overexpression enhanced the cell viability, clone formation and ADR-resistance of AML cells. ( A ) LINC00987 expression in MOLM13 and HL-60 cells were measured by RT-qPCR after transfection with pcDNA-LINC00987 and pcDNA-Empty at 24 h. ( B ) The proliferation of MOLM13 and HL-60 cells was detected by CCK8 after transfection with pcDNA-LINC00987 and pcDNA-Empty at 24 h under 0.2 µM ADR treatment. Then, the cell viability was calculated according to proliferation. ( C ) Clone formation was detected by soft agar assay colony formation. The number of cell clone formations was counted by imaging at 100x magnification. ( D ) The IC50 of ADR for the pcDNA-LINC00987-transfected MOLM13 and HL-60 cells were shown after different concentrations of ADR treatment at 24 h. ( E ) Under 0.2 µM ADR treatment, P-GP and BCRP expression in MOLM13 and HL-60 cells were measured by Western blot. ( F ) Apoptosis was detected by TUNEL staining and imaging at 400x magnification. *** P  < 0.001

LINC00987 functions as a ceRNA of miR-4458 to regulate ADR resistance in ADR-resistant AML cells

To examine the molecular mechanism of LINC00987 in AML cells, bioinformatics websites, including miRcord and LncBase Predicted v2, were used to analyze the potential miRNA sponges of LINC00987. The results revealed six miRNAs (Supplementary Fig.  3 A). qRT-PCR analysis demonstrated that miR-4458 expression in ADR/MOLM13 and ADR/HL-60 cells was abnormally reduced compared to that in MOLM13 and HL-60 cells, whereas the expression of the other five miRNAs was increased (Supplementary Fig.  3 B). These results suggest that only miR-4458 has a potential negative association with ADR resistance in AML. The binding sites of LINC00987 and miR-4458 were analyzed by GEPIA and luciferase reporter assay demonstrated that luciferase activities were significantly reduced between the LINC00987-wt + miR-4458 mimic group and the LINC00987-wt + NC mimic group. However, no obvious inhibitory effect between the LINC00987-mut + miR-4458 mimic group and the LINC00987-mut + NC mimic group was observed (Supplementary Fig.  3 C and 3 D). Anti-Ago2 RIP assay showed that LINC00987 and miR-4458 expression in ADR/MOLM13 and ADR/HL-60 cells was significantly enriched in the anti-Ago2 group compared with the anti-IgG group (Supplementary Fig.  3 E). Next, there is no significant correlation between the expression of LINC00987 and miR-4458 in AML patients (Supplementary Fig.  4 A). These results indicate that LINC00987 functions as a ceRNA of miR-4458.

To detect the effect of miR-4458 on ADR-resistant AML cells, ADR/MOLM13 and ADR/HL-60 cells were transfected with a miR-4458 mimic and then treated with 0.2 µM ADR. miR-4458 expression in ADR/MOLM13 and ADR/HL-60 cells was significantly enhanced after transfection with the miR-4458 mimic (Supplementary Fig.  5 A). Under 0.2 µM ADR treatment, the cell viability and the number of cell clone formation of ADR/MOLM13 and ADR/HL-60 cells in the miR-4458 mimic group was significantly lower than that in the NC mimic group (Supplementary Fig.  5 B and 5 5 C). The IC50 of miR-4458 mimic-transfected ADR/MOLM13 (0.27 µmol/L) and ADR/HL-60 (0.14 µmol/L) cells were visibly reduced compared with the IC50 of ADR/MOLM13 (2.40 µmol/L) and ADR/HL-60 (7.55 µmol/L) cells (Supplementary Fig.  5 D). More interestingly, P-GP and BCRP expression in the miR-4458 mimic group was clearly lower than that in the NC mimic group (Fig.  5 E).

Furthermore, to further clarify the relationship between LINC00987 and miR-4458 in ADR-resistant AML cells, si1-LINC00987 and the miR-4458 inhibitor were co-transfected into ADR/MOLM13 and ADR/HL-60 cells and then treated with 0.2 µM ADR. MiR-4458 expression in ADR/MOLM13 and ADR/HL-60 cells was significantly inhibited after co-transfection with si1-LINC00987 and the miR-4458 inhibitor (Fig.  5 A). Under 0.2 µM ADR treatment, the cell viability and the number of cell clone formations of ADR/MOLM13 and ADR/HL-60 cells co-transfected with si1-LINC00987 and the miR-4458 inhibitor was significantly higher than that in the co-transfected si1-LINC00987 and NC inhibitor group (Fig.  5 B and C). The IC50 of the si1-LINC00987 and miR-4458 inhibitor-co-transfected ADR/MOLM13 (1.1 µmol/L) and ADR/HL-60 (2.8 µmol/L) cells were noticeably increased compared with the IC50 of si1-LINC00987-transfected ADR/MOLM13 (0.16 µmol/L) and ADR/HL-60 (0.29 µmol/L) cells (Fig.  5 D). More interestingly, P-GP and BCRP expression in the co-transfected with si1-LINC00987 and the miR-4458 inhibitor was clearly higher than that in the co-transfected si1-LINC00987 and NC inhibitor group (Fig.  5 E).

miR-4458 regulates cell viability and ADR-resistance to affect LINC00987 function in ADR-resistant AML cells. ( A ) miR-4458 expression in ADR/MOLM13 and ADR/HL-60 cells were measured via RT-qPCR after co-transfection at 24 h. ( B ) The proliferation of ADR/MOLM13 and ADR/HL-60 cells was detected by CCK8 after co-transfection at 24 h under 0.2 µM ADR treatment. Then, the cell viability was calculated according to proliferation. ( C ) Clone formation of ADR/MOLM13 and ADR/HL-60 cells was detected by soft agar colony formation assay after co-transfection at 24 h under 0.2 µM ADR treatment. The number of cell clone formations was counted by imaging at 100× magnification. ( D ) The IC50 of ADR for co-transfected ADR/MOLM13 and ADR/HL-60 cells were shown after different concentrations of ADR treatment at 24 h. ( E ) Under 0.2 µM ADR treatment, P-GP and BCRP expression in ADR/MOLM13 and ADR/HL-60 cells were measured by western blotting after si1-LINC00987 and miR-4458 inhibitor co-transfection. *** P  < 0.001

miR-4458 inhibits HMGA2 expression to affect LINC00987 function in ADR-resistant AML cells

To examine the target of miR-4458 in ADR-resistant AML cells, bioinformatics websites (including Starbase 3.0, miRBD, and Targetscan 8.0) were used to analyze the potential targets of miR-4458. In addition, the top 100 genes that had a similar expression trend to LINC00987 in AML were analyzed using GEPIA. The intersections between the four sets of results were calculated; HMGA2 was found at this intersection (Supplementary Fig.  6 A). The binding sites of LINC00987 and miR-4458 are shown in Supplementary Fig.  6 B. In addition, luciferase reporter assays demonstrated that the luciferase activities were significantly reduced between the HMGA2 3’UTR-wt + miR-4458 mimic group and the HMGA2 3’UTR-wt + NC mimic group. However, there was no obvious inhibitory change between the HMGA2 3’UTR-mut + miR-4458 mimic group and HMGA2 3’UTR-mut + NC mimic group (Supplementary Fig.  6 C). These results showed that miR-4458 can bind to the HMGA2 3’-UTR in ADR/MOLM13 and ADR/HL-60 cells. In addition, HMGA2 protein expression in ADR/MOLM13 and ADR/HL-60 cells was notably reduced in the si-LINC00987 group compared to the si-NC group (Supplementary Fig.  6 D), while HMGA2 protein expression in MOLM13 and HL-60 cells was notably enhanced in the pcDNA-LINC00987 group compared to the pcDNA-Empty group (Supplementary Fig.  6 D). Moreover, HMGA2 protein expression in ADR/MOLM13 and ADR/HL-60 cells was notably enhanced in the si-LINC00987 + miR-4458 inhibitor group compared to the si-LINC00987 + NC inhibitor group, while it was notably reduced in the miR-4458 mimic group compared to the NC mimic group ( Supplementary Fig. 6E ). Next, there is no significant correlation between the expression of HMGA2 mRNA and miR-4458 in AML patients (Supplementary Fig.  4 B). These results showed that HMGA2 protein expression was inhibited by miR-4458 and promoted by LINC00987.

To further clarify the relationship between LINC00987 and HMGA2 in ADR-resistant AML cells, si1-LINC00987 and pcDNA-HMGA2 were co-transfected into ADR/MOLM13 and ADR/HL-60 cells and then treated with 0.2 µM ADR. HMGA2 expression in ADR/MOLM13 and ADR/HL-60 cells was significantly enhanced after co-transfection with si1-LINC00987 and pcDNA-HMGA2 (Fig.  6 A). Under 0.2 µM ADR treatment, the cell viability and the number of cell clone formations of ADR/MOLM13 and ADR/HL-60 cells in the co-transfected si1-LINC00987 and pcDNA-HMGA2 group was significantly higher than that in the co-transfected si1-LINC00987 and pcDNA-Empty group (Fig.  6 B and C). The IC50 of the si1-LINC00987 and pcDNA-HMGA2-co-transfected ADR/MOLM13 (2.35 µmol/L) and ADR/HL-60 (6.08 µmol/L) cells were evidently increased compared with the IC50 of the si1-LINC00987-transfected ADR/MOLM13 (0.13 µmol/L) and ADR/HL-60 (0.28 µmol/L) cells (Fig.  6 D). More interestingly, P-GP and BCRP expression in the co-transfected with si1-LINC00987 and pcDNA-HMGA2 was clearly higher than that in the co-transfected si1-LINC00987 and pcDNA-Empty group (Fig.  6 E).

HMGA2 promotes cell viability and ADR-resistance to assist in LINC00987 function in ADR-resistant AML cells. ( A ) HMGA2 protein expression in ADR/MOLM13 and ADR/HL-60 cells were measured by Western blot after si1-LINC00987 and pcDNA-HMGA2 co-transfection at 24 h. ( B ) The proliferation of ADR/MOLM13 and ADR/HL-60 cells was detected using CCK8 after co-transfection at 24 h under 0.2 µM ADR treatment. Then, the cell viability was calculated according to proliferation. ( C ) Clone formation of ADR/MOLM13 and ADR/HL-60 cells was detected by soft agar colony formation assay after co-transfection at 24 h under 0.2 µM ADR treatment. The number of cell clone formations was counted by imaging at 100× magnification. ( D ) The IC50 of ADR for co-transfected ADR/MOLM13 and ADR/HL-60 cells were shown after different concentrations of ADR treatment at 24 h. ( E ) Under 0.2 µM ADR treatment, P-GP and BCRP expression in ADR/MOLM13 and ADR/HL-60 cells were measured by western blotting after si1-LINC00987 and pcDNA-HMGA2 co-transfection. *** P  < 0.001

Only small number of aberrant lincRNA, such as LINC00239, has been found to regulate AML ADR-resistance according to experimentally and functionally validated [ 19 ]. Chemotherapy resistance is a major barrier in treating AML patients and improving outcomes in patients with AML [ 20 , 21 ]. Therefore, identifying targets to improve the chemoresistance of AML is of great significance for AML treatment. Herein, high LINC00987 expression was found in AML patients and indicates poor prognosis. In addition, our data demonstrated LINC00987 expression in ADR-resistance AML cell was higher than that in ADR-sensitive AML cell. Furthermore, LINC00987 downregulation reduced the proliferation, clone formation, IC 50, drug resistance proteins (P-GP and BCRP), and the volume of Xenograft tumor where promoted apoptosis under ADR treatment in ADR-resistance AML cell, while LINC00987 overexpression in ADR-sensitive AML cell played the opposite role. This study suggested that LINC00987 overexpression enhanced ADR-resistance. Furthermore, LINC00987 enhanced HMGA2 protein by sponging miR-4458 to contribute to ADR-resistance (Supplementary Fig.  7 ).

Recently, emerging studies had illustrated the oncogenic role of LINC00987 in breast cancer and osteosarcoma [ 22 , 23 ]. Importantly, high LINC00987 expression is associated with poor prognosis in AML patients [ 24 ]. The previous study was supported by our study indicating that LINC00987 expression was increased in AML patients and associated with poor prognosis using public databases analysis. Furthermore, this study firstly demonstrated that LINC00987 expression in ADR-resistance AML cell was prominently higher than that in ADR-sensitive AML cell, and LINC00987 downregulation reversed ADR-resistance in AML cells. Additionally, LINC00987 knockdown have been reported to inhibit the progression of AML cells via inhibiting proliferation and promoting apoptosis, showed that LINC00987 is an oncogene that promotes AML development [ 25 ]. Combined with our study, LINC00987 predicts poor prognosis, which is closely related not only to its ability to regulate the progression of AML, but also to its ability to regulate ADR-resistance in AML. This is the only study to clarify the function of LINC00987 in ADR-resistance, contributing to thestudy and promotion of LINC00987 in other ADR resistant cancers.

LincRNAs often act as endogenous ceRNAs to bind miRNAs by competing with miRNA-targeted genes [ 26 ]. For example, LINC00987 binds to miR-376a-5p by competing with FNBP1 to promote osteosarcoma cell development [ 23 ]. This study identified that LINC00987 acts as an endogenous sponge of miR-4458 in ADR-resistance AML cells. Emerging studies have illustrated that miR-4458 serves as the tumor suppressor miRNA in NSCLC, melanoma, and liver cancer by regulating tumorigenesis, epithelial-mesenchymal transition, and the immune microenvironment [ 27 , 28 , 29 ]. In addition, miR-4458 attenuates chemoresistance in NSCLC, breast cancer, and gastric cancer [ 30 , 31 , 32 ]. Similarly, our study showed that miR-4458 expression was reduced in ADR-resistance AML cell than that in ADR-sensitive AML cell and miR-4458 overexpression attenuated ADR resistance. Interestingly, miR-4458 expression is low in AML tissues, and miR-4458 downregulation promotes the proliferation and invasion of AML cells [ 33 ]. Combined with our study, miR-4458 inhibits the growth, development, and drug resistance of AML, making it an ideal target for the treatment of AML. In addition, this study also found that miR-4458 downregulation reversed the effect of LINC00987 knockdown on ADR resistance, suggesting that LINC00987 functions as a ceRNA of miR-4458 to regulate ADR resistance in ADR-resistant AML cells.

Finally, this study found that miR-4458 could bind to the 3’-UTR of HMGA2. Previous study found that HMGA2 is predominantly highly expressed in AML tissues and independently predicts poor prognosis in AML [ 34 ]. HMGA2 promotes cell proliferation, AML progression, and reduced chemosensitivity [ 35 , 36 ]. The results of those previous study were supported to the result of our study, which also indicate that HMGA2 overexpression enhanced ADR resistance in AML cells. Notably, HMGA2 expression was regulated by miRNA and lncRNA in many cancers [ 37 , 38 ]. Here, LINC00987 knockdown and miR-4458 overexpression reduced HMGA2 expression in ADR-resistance AML cell. Most importantly, HMGA2 overexpression reversed the effect of LINC09987 silencing in suppressing ADR resistance in ADR-resistant AML cells. This is the first study to reveal that HMGA2 was regulated by LINC09987/miR-4458 axis to enhance ADR resistance in AML cell.

Functionally, downregulation of LINC00987 weakens ADR resistance by releasing miR-4458 to deplete HMGA2 in AML cells. This study contributes to a better understanding of the function of LINC00987 in chemoresistance of AML cells. Therefore, this study showed new light on the regulation of ADR resistance and indicated that LINC00987 may serve as a therapeutic target for the treatment of chemoresistant AML cells.

Data availability

The data used and/or analyzed during the current study are included in this published article.

Abbreviations

• Acute myeloid leukemia

breast cancer resistance protein

competitive endogenous RNAs

high mobility group AT-hook 2

P glycoprotein

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Acknowledgements

This study was supported by the National Natural Science Foundation of China (No. 82073748 and 82373773), the Basic and Applied Basic Research Foundation of Guangdong Province (No. 2024A1515012921 and 2021A1515010993); Guang-dong Science and Technology Innovation Strategy Special fund (International science and technology cooperation projects) (No. 2021A0505030034), Guangdong Yiyang Healthcare Charity Foundation (JZ2024019), and Guangdong Provincial Science and Technology Program (2022B1111020003).

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Yue Liu and Xiao-ya Zhu contributed equally to this work.

Authors and Affiliations

Institute of Biomedicine, Department of Cellular Biology, Jinan University, No. 601 Huangpu Ave West, Shipai Street, Tianhe District, Guangzhou, Guangdong, 510632, China

Yue Liu & Yi Ma

State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, 430072, China

Xiao-ya Zhu

Research Center of Medical and Pharmaceutical Bioengineering, Minstry of Health, Guangdong Province Nucleic Acid Molecular Diagnostics Engineering Technology Research Center, Daan Gene Co Ltd, Guangzhou, 510663, China

Li-li Liao, Zhan-hui Zhang, Tao-sheng Huang & Xi-wen Jiang

Department of Hematology, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Shipai Street, Tianhe District, Guangzhou, 510630, China

National engineering research center of genetic Medicine, Key laboratory of Bioengineering Medicine of Guangdong Province, Guangzhou, 510632, China

The National Demonstration Center for Experimental Education of Life Science and Technology, Jinan University, Guangzhou, 510632, China

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Contributions

YL, XZ, LZ, XJ, and YM contributed to study conception and design, data analysis and interpretation of data; and YL drafted the manuscript and XZ revised the manuscript. LL, ZZ and TH contributions to experiment performed and data acquisition and analysis. LZ, XJ, and YM contributed to study conception and design, edited and revised manuscript, and provided financial support. All authors agree to submit this manuscript.

Corresponding authors

Correspondence to Ling Zhang , Xi-wen Jiang or Yi Ma .

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Liu, Y., Zhu, Xy., Liao, Ll. et al. Silencing LINC00987 ameliorates adriamycin resistance of acute myeloid leukemia via miR-4458/HMGA2 axis. Biol Direct 19 , 49 (2024). https://doi.org/10.1186/s13062-024-00490-1

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Received : 09 January 2024

Accepted : 12 June 2024

Published : 24 June 2024

DOI : https://doi.org/10.1186/s13062-024-00490-1

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