The Role of MicroRNAs in Myocardial Infarction: From Molecular Mechanism to Clinical Application

Sun, Tao; Dong, Yanhan; Du, Wei; Shi, Chun Ying; Wang, Kun; Tariq, Muhammad; Jx, Wang; Li, Peifeng

doi:10.3390/ijms18040745

Cited by 143 publications

(103 citation statements)

References 123 publications

(164 reference statements)

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“…Recently, dysregulation of miRNAs was reported in the development and progression of MI . miRNA‐29 was found to be decreased post‐MI, while miR‐21 was proved upregulated during cardiac stress .…”

Section: Discussionmentioning

confidence: 99%

lncRNA GAS5 regulates myocardial infarction by targeting the miR‐525‐5p/CALM2 axis

Zhang

Hou

Gao

et al. 2019

J of Cellular Biochemistry

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Long noncoding RNAs (lncRNAs) play critical roles in the pathogenesis of cardiovascular diseases, especially in myocardial infarction (MI). However, the underlying molecular mechanism of how lncRNA involves and affect MI still remains unclear. This study aimed to investigate the expression of lncRNA growth arrest‐specific transcript 5 (GAS5) and its effects on myocardial cells' proliferation, cell cycle, and apoptosis. The possible mechanisms involved in GAS5, calmodulin 2 (CALM2), and microRNA (miR)‐525‐5p were also explored. The messenger RNA (mRNA) level of CALM2, GAS5, and miR‐525‐5p in postmyocardial infarction (MI) and normal cells were examined by quantitative real‐time polymerase chain reaction (RT‐qPCR). Western blot analysis assay was conducted to detect the protein levels of CALM2. The changes of cell cycle/apoptosis and cell viability of post‐MI myocardial cells (PMMC) were determined by flow cytometry analysis and MTT (3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2H‐tetrazolium bromide) assay after knockdown of GAS5 or CALM2, respectively. Dual luciferase reporter assay and RNA‐binding protein immunoprecipitation (RIP) assay were performed to verify the targeting relationship between miR‐525‐5p and GAS5, CALM2 in myocardial. Hypoxic preconditioning was performed in normal cells, which constructed a simulated MI environment, and the effect of GAS5 on cardiomyocyte apoptosis was detected. Our data showed that the expression of GAS5 and CALM2 in PMMC was significantly upregulated, while the expression of miR‐525‐5p was downregulated. Overexpression of GAS5 and CALM2 profoundly promoted the apoptosis of myocardial cell. However, the proliferation of myocardial cell was inhibited by the upregulation of GAS5 and CALM2. Moreover, GAS5 was proved to be the target of miR‐525‐5p and GAS5 downregulated the expression of miR‐525‐5p and CALM2. In addition, lncRNA GAS5 promotes MI, while CALM2 induced MI can be reversed by miR‐525‐5p. These data suggested that lncRNA GAS5 promoted the development and progression of MI via targeting of the miR‐525‐5p/CALM2 axis and it has the potential to be explored as a therapeutic target for the treatment of MI in the future.

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Section: Discussionmentioning

confidence: 99%

lncRNA GAS5 regulates myocardial infarction by targeting the miR‐525‐5p/CALM2 axis

Zhang

Hou

Gao

et al. 2019

J of Cellular Biochemistry

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“…In recent years, several cardiac-specific miRNAs have been identified to play important roles in the development of cardiovascular diseases 69. Among these miRNAs, four cardiac-enriched miRNAs (miR-208, miR-499, miR-1 and miR-133) are consistently found to be increased in the plasma of patients with AMI 70.…”

Section: Summary Of Cardiac Biomarkersmentioning

confidence: 99%

Diagnostic and prognostic value of biomarkers in acute myocardial infarction

Chen

Tao

Zhang

et al. 2019

Postgraduate Medical Journal

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The incidence of acute myocardial infarction (AMI) has been increasing rapidly in recent years, seriously endangering human health. Cardiac biomarkers play critical roles in the diagnosis and prognosis of AMI. Troponin is a highly sensitive and specific biomarker for AMI diagnosis and can independently predict adverse cardiac events. Other biomarkers such as N-terminal B-type natriuretic peptide and C reactive protein are also valuable predictors of cardiovascular prognosis. Recently, several novel biomarkers have been identified for the diagnosis and risk assessment in patients with AMI. A multibiomarker approach can potentially enhance the diagnostic accuracy and provide more information for the early risk stratification of AMI. In this review, we will summarise the biomarkers discovered in recent years and focus on their diagnostic and prognostic value for patients with AMI.

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“…The human genome is enriched with polymorphisms that result in different phenotypes. Accumulating evidence suggests that miRNAs play important regulatory roles in different diseases including cardiovascular disease . The polymorphisms in miRNAs have been linked to susceptibility to cardiovascular diseases such as myocardial infarction and coronary heart disease .…”

Section: Discussionmentioning

confidence: 99%

“…As miR‐499‐5p is highly expressed in cardiac tissue and participates in the maintenance of cardiac survival and function, it is reasonable to propose that polymorphism rs3746444 may contribute to the susceptibility of heart diseases. For the polymorphism rs3746444 (A→G) of hsa‐mir‐499, the few previous studies have shown that the variant genotype GG of this SNP was significantly associated with the increased risk of cancer and dilated cardiomyopathy, but most of the studies found no significant association with the increased risk of cancer .…”

Section: Discussionmentioning

confidence: 99%

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A polymorphism rs3746444 within the pre‐miR‐499 alters the maturation of miR‐499‐5p and its antiapoptotic function

Ding

Sun

et al. 2018

J Cellular Molecular Medi

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AbstractmicroRNAs (miRNAs) are non‐coding RNAs that function as post‐transcriptional regulators of cardiac development and cardiovascular diseases. Single nucleotide polymorphisms (SNPs) in miRNA genes are a novel class of genetic variations in the human genome that confer the risk of cardiovascular diseases. Here, we identified a polymorphism A→G (rs3746444) in miR‐499 precursor (pre‐miR‐499) that affects the maturation of miR‐499‐5p and alters its antiapoptotic function by converting stable A‐U base pair to wobble G‐U base pair in pre‐miR‐499 secondary structure. Furthermore, our results showed that the concentrations of plasma miR‐499‐5p could be correlated with myocardial infarction (MI) and heart failure (HF) patients in comparison with control subjects and polymorphism rs3746444 in miR‐499 could influence its abundance in plasma. Finally, our results also showed that the variant of polymorphism in miR‐499 influenced the severity of the myocardial infarction significantly. This is the first report to highlight the biological significance of this polymorphism on the maturation of miR‐499‐5p and its antiapoptotic role during MI. These findings may pave a way to better understand the individual variability based on miRNA SNPs in heart diseases and may contribute to better treatment for disease severity on a personalized level.

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The Role of MicroRNAs in Myocardial Infarction: From Molecular Mechanism to Clinical Application

Cited by 143 publications

References 123 publications

lncRNA GAS5 regulates myocardial infarction by targeting the miR‐525‐5p/CALM2 axis

lncRNA GAS5 regulates myocardial infarction by targeting the miR‐525‐5p/CALM2 axis

Diagnostic and prognostic value of biomarkers in acute myocardial infarction

A polymorphism rs3746444 within the pre‐miR‐499 alters the maturation of miR‐499‐5p and its antiapoptotic function

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