MicroRNA-155 Promotes Myocardial Infarction-Induced Apoptosis by Targeting RNA-Binding Protein QKI

Abstract

Acute myocardial infarction (AMI) is the leading cause of sudden death worldwide. MicroRNA-155 (miR-155) has been reported to target antiapoptotic genes in various diseases models, but the functional role of miR-155 in response to MI injury needs further investigations. This study investigated the role of miR-155 in myocardial ischemia injury. TUNEL and flow cytometry were performed to measure cell apoptosis. Western blot analysis was employed to detect protein expressions of Bcl-2, XIAP, Bax, and caspase-3. qRT-PCR was used to quantify miRNA levels. We showed that miR-155 was dynamically elevated in murine hearts subjected to MI and in neonatal rat ventricular cardiomyocyte (NRVM) injury induced by hydrogen peroxide (H2O2). In response to H2O2, the silencing of miR-155 using AMO-155 (antisense inhibitor oligodeoxyribonucleotides) significantly increased cell viability and reduced cell apoptosis. Moreover, AMO-155 reversed the H2O2-induced downregulation of Bcl-2 and XIAP and upregulation of Bax and cleaved-caspase-3. Further study revealed that AMO-155 resulted in a decrease of H2O2-induced JC-1-labelled monomeric cell number. In addition, AMO-155 markedly decreased infarct size, ameliorated impaired cardiac function, and significantly reduced apoptotic cell percentages in MI mice heart. The RNA-binding protein Quaking (QKI) was predicted as a target gene of miR-155 through bioinformatic analysis, and AMO-155 attenuated the downregulation of QKI in H2O2-treated cardiomyocytes and MI mice heart. Knockdown of QKI by siRNA abolished the antiapoptotic effects of AMO-155. Taken together, miR-155 is upregulated in the MI heart and NRVMs in response to H2O2 stress, and downregulating of miR-155 protects cardiomyocytes against apoptosis. Mechanistically, it is probably due to the repression of QKI signaling pathway.

microRNA-155 Is Decreased During Atherosclerosis Regression and Is Increased in Urinary Extracellular Vesicles During Atherosclerosis Progression

“…This is in keeping with other studies which showed the regulatory effects of miR-155 on BCL-2 and cardiac apoptosis in a murine model of LPS-induced cardiac dysfunction (60). miR-155 inhibition prevented the downregulation of H 2 O 2 induced BCL-2 in cardiomyocytes and was protective against ischemia-induced apoptosis in vivo (61). In contrast, BMDMs lacking miR-155 were more susceptible to apoptosis during infection, suggesting that miR-155 has an antiapoptotic function (62).…”

Predicting Diagnostic Gene Biomarkers Associated With Immune Infiltration in Patients With Acute Myocardial Infarction

“…Acute myocardial infarction (AMI) is a common event in coronary heart disease that results from interrupted blood flow to a certain area of the heart. It is considered one of the primary causes of disability and death from cardiovascular disease worldwide, and is a leading health threat in humans (1). AMI remains the primary cause of morbidity and mortality worldwide, with ∼7 million patients diagnosed with AMI each year (2,3).…”

A Computational Model to Predict the Causal miRNAs for Diseases

“…We found that hsa-mir-155 has a score of 0.243 and is ranked first out of all potential miRNAs ( Table 1 ). And the causal association between mir-155 and MI has been verified in the latest literature that has not been recorded in HMDD v3.1 (Guo et al, 2019). In this article, researchers found that the expression of miR-155 was dynamically upregulated in murine hearts subjected to MI, and the inhibition of miR-155 expression with AMO-155 (an antisense inhibitor oligodeoxyribonucleotides against miR-155) could significantly increase cell viability, reduce cell apoptosis, and improve the cardiac function.…”