title: Extracellular vesicles-mediated transfer of miR-208a/b exaggerate hypoxia/reoxygenation injury in cardiomyocytes by reducing QKI expression.
abstract: In this study, we tested the hypothesis that extracellular vesicles (EVs)-mediated transfer of miR-208a/b can exacerbate apoptosis of cardiomyocytes (CMs) induced by hypoxia/reoxygenation (H/R) injury by reducing the expression of the RNA-binding protein Quaking (QKI). EVs were isolated from culture medium of hypoxic H9c2 cells (EVs-H). In in vitro H9c2 cell model, the EVs-H could be taken up by normoxic CMs and exacerbated cell apoptosis induced by H/R injury. In addition, miR-208a and miR-208b were enriched in EVs-H. Suppression of miR-208a and miR-208b loading significantly suppressed the detrimental effect of EVs-H on H/R injury in H9c2 cells. Inhibition of endogenous miR-208a and miR-208b restored QKI5 and QKI6 after H/R treatment. Dual-luciferase assay confirmed direct bindings between miR-208a/b and QKI 3'UTR. Functionally, QKI5 overexpression significantly suppressed H/R-induced CM apoptosis and suppressed the enhancing effect of EVs-H on CM apoptosis. Therefore, we infer that EVs-mediated transfer of miR-208a/b can exaggerate H/R injury in CMs by reducing QKI expression. This represents a previously unrecognized pathway of H/R injury in CMs.
authors.affiliation: The 7th Department of Internal Medicine (Department of Geriatric Cardiovascular and Cerebrovascular Diseases), Zaozhuang Hospital of Zaozhuang Mining Group, Zaozhuang, 277100, Shandong, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Zoucheng People's Hospital, Zoucheng, 273500, Shandong, China.
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Nursing, Binzhou People's Hospital, Binzhou, 256600, Shandong, China.
authors.forename: Pirong
authors.initials: P
authors.lastname: Yang
authors.affiliation: Department of Preventive Health Care, Weifang No.2 People's Hospital, Weifang, 261000, Shandong, China. xialia1@outlook.com.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D002460:Cell Line; D055252:Cell-Derived Microparticles / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D035683:MicroRNAs / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D016601:RNA-Binding Proteins / Q000096:biosynthesis*; D051381:Rats
chemical_list: C569395:MIRN208 microRNA, rat; D035683:MicroRNAs; C522776:Qk protein, rat; D016601:RNA-Binding Proteins
keywords: Cardiomyocyte; Extracellular vesicles; Hypoxia/reoxygenation; MiR-208; QKI