miR-378a-3p inhibits ischemia/reperfusion-induced apoptosis in H9C2 cardiomyocytes by targeting TRIM55 via the DUSP1-JNK1/2 signaling pathway.

Abstract

MicroRNAs (miRNAs) are involved in many pathological and biological processes, such as ischemia/reperfusion (I/R) injury by modulating gene expression. Increasing evidence indicates that miR-378a-3p might provide a potential cardioprotective effect against ischemic heart disease. Cell apoptosis is a crucial mechanism in I/R injury. As such, this study evaluated the protective effects and underlying mechanisms of action of miR-378a-3p on H9C2 cardiomyocyte apoptosis following I/R injury. We found that I/R-induced H9C2 cardiomyocytes exhibited a decrease in miR-378a-3p expression, while treatment with a miR-378a-3p mimic suppressed cell apoptosis, JNK1/2 activation, cleavage of PARP and caspase-3, and Bax/Bcl-2 ratio but increased DUSP1 expression, which subsequently inhibited JNK1/2 phosphorylation. TRIM55 was shown to be a target of miR-378a-3p and its downregulation inhibited the miR-378a-3p inhibitor-induced increase in cell apoptosis and JNK1/2 activation. TRIM55 inhibited DUSP1 protein expression through ubiquitination of DUSP1. Moreover, DUSP1 overexpression inhibited the TRIM55 overexpression-induced increase in cell apoptosis and JNK1/2 activation. The protective effect of miR-378a-3p was subsequently confirmed in a rat myocardial I/R model, as evidenced by a decrease in cardiomyocyte apoptosis of cardiomyocytes, TRIM55 expression, and JNK1/2 activation. Taken together, these results suggest that miR-378a-3p may protect against I/R-induced cardiomyocyte apoptosis via TRIM55/DUSP1/JNK signaling.

• Authors: Jiaying Tan, Jun Shen, Huigeng Zhu, Ye Gong, Hechen Zhu, Junping Li, Shan Lin, Gang Wu, Tao Sun
• Journal: Aging (Aging (Albany NY)) Vol. 12 Issue 10 Pg. 8939-8952 (05 28 2020) ISSN: 1945-4589 [Electronic] United States
• PMID: 32463795 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• MIRN378 microRNA, rat
• MicroRNAs
• Muscle Proteins
• Trim55 protein, rat
• Tripartite Motif Proteins
• Ubiquitin-Protein Ligases
• Mitogen-Activated Protein Kinase 8
• Dual Specificity Phosphatase 1
• Dusp1 protein, rat

Topics

• Animals
• Apoptosis (genetics)
• Cell Line
• Dual Specificity Phosphatase 1 (metabolism)
• MAP Kinase Signaling System (genetics)
• MicroRNAs (genetics, metabolism)
• Mitogen-Activated Protein Kinase 8 (metabolism)
• Muscle Proteins (genetics, metabolism)
• Myocytes, Cardiac (cytology, drug effects)
• Rats
• Reperfusion Injury (metabolism)
• Tripartite Motif Proteins (genetics, metabolism)
• Ubiquitin-Protein Ligases (genetics, metabolism)