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MiR-499 protects cardiomyocytes from H 2O 2-induced apoptosis via its effects on Pdcd4 and Pacs2.


ABSTRACT: Background microRNAs (miRNAs) are a class of small, non-coding endogenous RNAs that post-transcriptionally regulate some protein-coding genes. miRNAs play an important role in many cardiac pathophysiological processes, including myocardial infarction, cardiac hypertrophy, and heart failure. miR-499, specifically expressed in skeletal muscle and cardiac cells, is differentially regulated and functions in heart development. However, the function of miR-499 in mature heart is poorly understood. Results We report that cardiac-abundant miR-499 could protect neonatal rat cardiomyocytes against H 2O 2-induced apoptosis. Increased miR-499 level favored survival, while decreased miR-499 level favored apoptosis. We identified three proapoptotic protein-coding genes-Pdcd4, Pacs2, and Dyrk2-as targets of miR-499. miR-499 inhibited cardiomyocyte apoptosis through its suppressive effect on Pdcd4 and Pacs2 expression, thereby blocking Bid expression and BID mitochondrial translocation. We also found that H 2O 2-induced phosphorylation of c-Jun transcriptionally upregulated miR-499 expression via binding of phosphorylated c-Jun to the Myh7b promoter. Conclusions Our results revealed that miR-499 played an inhibiting role in the mitochondrial apoptosis pathway, and had protective effects against H 2O 2-induced injury in cardiomyocytes.

SUBMITTER: Wang J 

PROVIDER: S-EPMC4075519 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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miR-499 protects cardiomyocytes from H 2O 2-induced apoptosis via its effects on Pdcd4 and Pacs2.

Wang Jiaji J   Jia Zhuqing Z   Zhang Chenguang C   Sun Min M   Wang Weiping W   Chen Ping P   Ma Kangtao K   Zhang Youyi Y   Li Xianhui X   Zhou Chunyan C  

RNA biology 20140227 4


Background microRNAs (miRNAs) are a class of small, non-coding endogenous RNAs that post-transcriptionally regulate some protein-coding genes. miRNAs play an important role in many cardiac pathophysiological processes, including myocardial infarction, cardiac hypertrophy, and heart failure. miR-499, specifically expressed in skeletal muscle and cardiac cells, is differentially regulated and functions in heart development. However, the function of miR-499 in mature heart is poorly understood. Res  ...[more]

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