miR‐496 remedies hypoxia reoxygenation–induced H9c2 cardiomyocyte apoptosis via Hook3‐targeted PI3k/Akt/mTOR signaling pathway activation

Abstract

The hypoxia‐reoxygenation (H/R) model helps analyze myocardial infarction triggered by acute myocardial ischemia, which induces cardiomyocyte proliferation and apoptosis. The Gene Expression Omnibus database was used to obtain the GSE74205 and GSE3866 microarray data, including microRNA (miRNA) and messenger RNA profiles, to catalog potential key miRNAs and genes. The role of rno‐mir‐496 expression in cardiomyocyte proliferation within 10 days of birth was established. The microRNA Target Prediction Database (miRDB) database—via Gene Ontology annotation—predicted hook microtubule tethering protein 3 (Hook3), a key target gene of rno‐mir‐496, was closely related to cell proliferation. Upregulation of miR‐496 related to a significant reduction in apoptosis of H9c2 and human cardiomyocytes treatment with H/R. Moreover, transfection of H9c2 cells with miR‐496 mimics, which were pretreated with H/R for 12 hours, increased Ki67 levels, proliferating cell nuclear antigen and Bcl‐2 proteins; and decreased cleaved caspase‐3 and Bax protein levels, as determined by reverse transcription‐polymerase chain reaction and Western blot assays. A dual‐luciferase reporter system confirmed that miR‐496 targets the Hook3 suppressor. Hook3 overexpression stimulated apoptosis in H/R‐treated cells, thus reducing cell proliferation. Upregulated miR‐496 activated phosphatidylinositol‐3‐kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling, while Hook3 exhibited the inverse trend in H/R‐treated H9c2 cells. In summary, with Hook3 functionality's aid, miR‐496 upregulation defends cells from H/R‐induced apoptosis and stimulates cell proliferation. miR‐496 targets Hook3 to trigger the PI3K/Akt/mTOR signaling pathway for antiapoptotic and proliferative effects.

Expression of miRNAs in plasma exosomes derived from patients with atrial fibrillation

“…*P < .005 vs SR group cardiovascular diseases via the above signaling pathways. 35 In addition, AF can lead to a wide range of abnormalities, including changes in the local myocardial microenvironments, inflammatory responses, mitochondrial dysfunction, abnormal lipid metabolism, and further facilitate the initiation and maintenance of AF, [36][37][38] meanwhile, the enrichment analysis in this experiment has also confirmed the role of miRNAs in the formation of mechanisms of AF via the above mechanisms. Therefore, miRNAs in the serum are able to participate in the formation of mechanisms of AF through various factors, and meanwhile, the results of this enrichment analysis can provide research directions for further exploring the specific mechanisms of miRNAs affecting the initiation of AF.…”

“…Jin et al also found that miR‐496 was able to remedy hypoxia‐induced cardiomyocyte apoptosis via PI3k/Akt/mTOR signaling pathways. The above demonstration indicated that MAPK and mTOR signaling pathways play an essential role in the progression of cardiovascular diseases, and at the same time, various miRNAs inside human body play significant a role in the progression of cardiovascular diseases via the above signaling pathways 35 . In addition, AF can lead to a wide range of abnormalities, including changes in the local myocardial microenvironments, inflammatory responses, mitochondrial dysfunction, abnormal lipid metabolism, and further facilitate the initiation and maintenance of AF, 36‐38 meanwhile, the enrichment analysis in this experiment has also confirmed the role of miRNAs in the formation of mechanisms of AF via the above mechanisms.…”

The Circular RNA circRNA124534 Promotes Osteogenic Differentiation of Human Dental Pulp Stem Cells Through Modulation of the miR-496/β-Catenin Pathway

“…Therefore, miRNAs play an important role in the regulation of stem cell osteogenic differentiation. Aberrant expression of miR-125a-5p has been observed in various diseases, including myocardial infarction (Jin and Ni, 2019), atherosclerosis (Hu et al, 2019), cerebral injury (Yao et al, 2019), diabetes (Rubie et al, 2019), and various malignant tumors (Mason et al, 2018;Ma et al, 2019;Wang et al, 2019). Inhibition of miR-496 has been found to reverse the inhibitory effects of IL-1β in bone marrow stem cell-associated bone regeneration (Huang and Chen, 2017).…”

MiR-486 protects against acute myocardial infarction via regulation of PTEN

“…An in vivo study on myocardial infarction in rats indicated that increased expression of miR-133a can reduce the mRNA and protein levels of TGF-β1 and CTGF after myocardial infarction, decreasing myocardial collagen deposition, inhibiting myocardial fibrosis and improving heart function [6]. In addition, a study suggested that miR-496 is able to resist myocardial apoptosis by targeting Hook3 and activating the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR signaling pathway [7].…”