title: miR-133a mediates the hypoxia-induced apoptosis by inhibiting TAGLN2 expression in cardiac myocytes.
abstract: Myocardial hypoxia is a major cause of cardiac dysfunction due to its triggering cell injury and apoptosis. Deregulated microRNAs and their roles in cardiomyocyte apoptosis have attracted much attention. miR-133a is among the most abundant of the miRNAs present in the normal heart, and significant changes in expression of miR-133a were observed in response to anoxia stress. However, the role of this microRNA in myocardial hypoxia-induced apoptosis is presently unclear. In this study, we identified that miR-133a expression was down-regulated in hypoxic H9c2 cells, and its expression gradually decreased with hypoxia time. Functional analysis revealed that miR-133a attenuated hypoxia-induced apoptosis. We further detected expression of apoptosis-related proteins. The results showed that miR-133a suppressed the expression of apoptotic proteins caspase-8, caspase-9, and caspase-3 significantly, while improved the expression of Bcl-2. Bioinformatics analysis, combined with dual-luciferase reporter analysis, was applied to determine that miR-133a directly was binded to the 3'-untranslated region (3'-UTR) of TAGLN2 mRNA and suppressed expression at both transcriptional and translational levels. Next, TAGLN2 knockout was used to reveal that TAGLN2 modulated hypoxia-induced apoptosis via caspase-8 apoptotic pathway. Taken together, our data demonstrated the roles of miR-133a in hypoxia-induced apoptotic and implicate its potential in cardiac dysfunctions therapy.
authors.affiliation: Department of Cardiology, The Third Xiangya Hospital of Central South University, No.138, Tongzipo Road, Yuelu District, Changsha, 410013, Hunan Province, China.
authors.forename: An-Ying
authors.initials: AY
authors.lastname: Li
authors.forename: Qiong
authors.initials: Q
authors.lastname: Yang
authors.forename: Kan
authors.initials: K
authors.lastname: Yang
mesh_terms: D017209:Apoptosis / Q000235:genetics; D053181:Caspase 8 / Q000096:biosynthesis; D015687:Cell Hypoxia / Q000235:genetics*; D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D008840:Microfilament Proteins / Q000096:biosynthesis / Q000235:genetics*; D009124:Muscle Proteins / Q000096:biosynthesis / Q000235:genetics*; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology*
chemical_list: C548234:MIRN133 microRNA, human; D035683:MicroRNAs; D008840:Microfilament Proteins; D009124:Muscle Proteins; C585387:Tagln2 protein, human; D053181:Caspase 8