Junxi Liao, Chan Li, Min Zheng, Ruizheng Shi, Zhaoya Liu
Cardiac aging is the major risk factor and important pathogenic foundation for cardiovascular diseases (CVDs) in the elderly. Various miRNAs have been reported to participate in this process. However, the precise mechanisms through which distinct miRNAs contribute to cardiac aging remain to be fully elucidated. In this study, micro-RNA sequencing (miRNA-seq) was performed on hearts of 5-month-old and 22-month-old C57BL/6 mice, revealing a decreased expression of miR-378d in the hearts of aged mice. Dual-luciferase reporter assay confirmed that SH3GL2 serves as a target gene of miR-378d in aging heart. In vitro, SH3GL2 was upregulated in senescent AC-16 cardiomyocytes treated with 200 μM H2O2 for 24 h. Knockdown of SH3GL2 ameliorated H2O2-induced senescence of cardiomyocytes. Further experiments confirmed that SH3GL2 regulated the production of reactive oxygen species (ROS) through Calpain-1, and knockdown of SH3GL2 can partially reverse miR-378d inhibitor-induced cardiomyocyte senescence. Collectively, our study demonstrated that miR-378d is decreased in aging heart and may induce cardiomyocyte senescence via calpain-1/ROS pathway by targeting SH3GL2 directly.