caa a22 4500 606236422 CHVBK 20210128101247.0 cr unu---uuuuu 210128e20150201xx s 000 0 eng 10.1007/s11010-014-2273-2 doi (NATIONALLICENCE)springer-10.1007/s11010-014-2273-2 miR-133a mediates the hypoxia-induced apoptosis by inhibiting TAGLN2 expression in cardiac myocytes [Elektronische Daten] [An-ying Li, Qiong Yang, Kan Yang] 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. Springer Science+Business Media New York, 2014 Cardiomyocyte nationallicence Hypoxia-induced apoptosis nationallicence MiR-133a nationallicence TAGLN2 nationallicence miRNA : microRNA nationallicence miR-133a : microRNA-133a nationallicence UTR : Untranslated region nationallicence TAGLN2 : Transgelin 2 nationallicence Li An-ying Department of Cardiology, The Third Xiangya Hospital of Central South University, No.138, Tongzipo Road, Yuelu District, 410013, Changsha, Hunan Province, China aut Yang Qiong Department of Cardiology, The Third Xiangya Hospital of Central South University, No.138, Tongzipo Road, Yuelu District, 410013, Changsha, Hunan Province, China aut Yang Kan Department of Cardiology, The Third Xiangya Hospital of Central South University, No.138, Tongzipo Road, Yuelu District, 410013, Changsha, Hunan Province, China aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 400/1-2(2015-02-01), 173-181 0300-8177 400:1-2<173 2015 400 11010 https://doi.org/10.1007/s11010-014-2273-2 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-014-2273-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Li An-ying Department of Cardiology, The Third Xiangya Hospital of Central South University, No.138, Tongzipo Road, Yuelu District, 410013, Changsha, Hunan Province, China aut NATIONALLICENCE 700 1- Yang Qiong Department of Cardiology, The Third Xiangya Hospital of Central South University, No.138, Tongzipo Road, Yuelu District, 410013, Changsha, Hunan Province, China aut NATIONALLICENCE 700 1- Yang Kan Department of Cardiology, The Third Xiangya Hospital of Central South University, No.138, Tongzipo Road, Yuelu District, 410013, Changsha, Hunan Province, China aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 400/1-2(2015-02-01), 173-181 0300-8177 400:1-2<173 2015 400 11010