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miR-133a mediates the hypoxia-induced apoptosis by inhibiting TAGLN2 expression in cardiac myocytes

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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.

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Abbreviations

miRNA:

microRNA

miR-133a:

microRNA-133a

UTR:

Untranslated region

TAGLN2:

Transgelin 2

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Authors and Affiliations

  1. Department of Cardiology, The Third Xiangya Hospital of Central South University, No.138, Tongzipo Road, Yuelu District, Changsha, 410013, Hunan Province, China

    An-ying Li, Qiong Yang & Kan Yang

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  1. An-ying Li
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  2. Qiong Yang
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  3. Kan Yang
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Correspondence to Kan Yang.

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Li, Ay., Yang, Q. & Yang, K. miR-133a mediates the hypoxia-induced apoptosis by inhibiting TAGLN2 expression in cardiac myocytes. Mol Cell Biochem 400, 173–181 (2015). https://doi.org/10.1007/s11010-014-2273-2

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  • DOI: https://doi.org/10.1007/s11010-014-2273-2

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