title: Overexpression of Exosomal Cardioprotective miRNAs Mitigates Hypoxia-Induced H9c2 Cells Apoptosis.
abstract: Recent evidence suggests that hypoxia caused by acute myocardial infarction can induce cardiomyocyte apoptosis. Exosomes are signalling mediators that contribute to intercellular communication by transporting cytosolic components including miRNAs, mRNAs, and proteins. However, the systemic regulation and function of exosomal miRNAs in hypoxic cardiomyocytes are currently not well understood. Here, we used small RNA sequencing to investigate the effects of hypoxia stress on miRNAome of rat cardiomyoblast cells (H9c2) and corresponding exosomes. We identified 92 and 62 miRNAs in cells and exosomes, respectively, that were differentially expressed between hypoxia and normoxia. Hypoxia strongly modulated expression of hypoxia-associated miRNAs in H9c2 cells, and altered the miRNAome of H9c2 cells-derived exosomes. Functional enrichment analysis revealed extensive roles of differentially expressed exosomal miRNAs in the HIF-1 signalling pathway and in apoptosis-related pathways including the TNF, MAPK, and mTOR pathways. Furthermore, gain- and loss-of-function analysis demonstrated potential anti-apoptotic effects of the hypoxia-induced exosomal miRNAs, including miR-21-5p, miR-378-3p, miR-152-3p, and let-7i-5p; luciferase reporter assay confirmed thatAtg12andFaslgare targets of miR-152-3p and let-7i-5p, respectively. To summarize, this study revealed that hypoxia-induced exosomes derived from H9c2 cells loaded cardioprotective miRNAs, which mitigate hypoxia-induced H9c2 cells apoptosis.
authors.affiliation: Institute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, Sichuan, China. Jinweizhang50@163.com.
authors.forename: Jinwei
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Institute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, Sichuan, China. jideng_ma@sina.com.
authors.forename: Jideng
authors.initials: J
authors.lastname: Ma
authors.affiliation: Institute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, Sichuan, China. longkeren@163.com.
authors.forename: Keren
authors.initials: K
authors.lastname: Long
authors.affiliation: Institute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, Sichuan, China. qiuwanling2016@163.com.
authors.forename: Wanling
authors.initials: W
authors.lastname: Qiu
authors.affiliation: Institute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, Sichuan, China. wangyujie715@163.com.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Institute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, Sichuan, China. Huzihui2016@163.com.
authors.forename: Zihui
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Institute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, Sichuan, China. 18227550880@163.com.
authors.forename: Can
authors.initials: C
authors.lastname: Liu
authors.affiliation: Institute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, Sichuan, China. luoyi670@163.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Institute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, Sichuan, China. lingdang317@163.com.
authors.forename: Anan
authors.initials: A
authors.lastname: Jiang
authors.affiliation: Institute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, Sichuan, China. longjin8806@163.com.
authors.forename: Long
authors.initials: L
authors.lastname: Jin
authors.affiliation: Institute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, Sichuan, China. wupie@163.com.
authors.forename: Qianzi
authors.initials: Q
authors.lastname: Tang
authors.affiliation: Institute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, Sichuan, China. xun_wang007@163.com.
authors.forename: Xun
authors.initials: X
authors.lastname: Wang
authors.affiliation: Institute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, Sichuan, China. xuewei.li@sicau.edu.cn.
authors.forename: Xuewei
authors.initials: X
authors.lastname: Li
authors.affiliation: Institute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, Sichuan, China. mingzhou.li@163.com.
authors.forename: Mingzhou
authors.initials: M
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis; D015687:Cell Hypoxia; D002460:Cell Line; D055354:Exosomes / Q000235:genetics*; D005786:Gene Expression Regulation; D051793:Hypoxia-Inducible Factor 1 / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics*; D032386:Myoblasts, Cardiac / Q000166:cytology*; D051381:Rats; D017423:Sequence Analysis, RNA / Q000379:methods*; D015398:Signal Transduction
chemical_list: D051793:Hypoxia-Inducible Factor 1; D035683:MicroRNAs
keywords: H9c2 cells; apoptosis; exosome; hypoxia; microRNA