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.

• Authors: Jiaji Wang, Zhuqing Jia, Chenguang Zhang, Min Sun, Weiping Wang, Ping Chen, Kangtao Ma, Youyi Zhang, Xianhui Li, Chunyan Zhou
• Journal: RNA biology (RNA Biol) Vol. 11 Issue 4 Pg. 339-50 ( 2014) ISSN: 1555-8584 [Electronic] United States
• PMID: 24646523 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apoptosis Regulatory Proteins
• BH3 Interacting Domain Death Agonist Protein
• MIRN499 microRNA, rat
• MicroRNAs
• Pacs2 protein, rat
• Pdcd4 protein, rat
• Proto-Oncogene Proteins c-jun
• RNA, Messenger
• Reactive Oxygen Species
• Vesicular Transport Proteins
• Hydrogen Peroxide
• Dyrk kinase
• Protein-Tyrosine Kinases
• Protein Serine-Threonine Kinases

Topics

• Animals
• Animals, Newborn
• Apoptosis (drug effects, genetics)
• Apoptosis Regulatory Proteins (genetics)
• BH3 Interacting Domain Death Agonist Protein (genetics, metabolism)
• Gene Expression Profiling
• Gene Expression Regulation
• Hydrogen Peroxide (pharmacology)
• Male
• MicroRNAs (genetics)
• Myocytes, Cardiac (drug effects, metabolism)
• Phosphorylation
• Protein Serine-Threonine Kinases (genetics)
• Protein-Tyrosine Kinases (genetics)
• Proto-Oncogene Proteins c-jun (metabolism)
• RNA Interference
• RNA, Messenger
• Rats
• Reactive Oxygen Species
• Vesicular Transport Proteins (genetics)