Jie Lin, Haihuan Lin, Chao Ma, Fengquan Dong, Yingchun Hu, Haiying Li
Department of Cardiology, Shenzhen University General Hospital, Shenzhen, Guandong, China (mainland)
Med Sci Monit 2019; 25:8733-8743
MicroRNAs (miRNAs), which modulate the expression of their target genes, are commonly involved in stimulating and adjusting of many processes that result in cardiovascular diseases, contain cardiac ischemia/reperfusion (I/R) damage. However, the expression and role of miR-149 in pyroptosis mediated myocardial I/R damage remains unclear.
MATERIAL AND METHODS: Real-time polymerase chain reaction was performed to measure the miR-149 and FoxO3 expression in I/R stimulated H9C2 cells. The cell proliferation, pyroptosis-related inflammatory genes in I/R-treated H9C2 cells transfected miR-149 mimics or miR-149 inhibitor were both explored. We predicted and confirmed miR-149 targets by using bioinformatics analyses and luciferase reporter assay. In addition, the potential relationship between miR-149 and FoxO3 in pyroptosis from I/R treated H9C2 cells was analyzed.
RESULTS: Our results showed that miR-149 was upregulated, while FoxO3 was downregulated in I/R stimulated H9C2 cells. Over-expression of miR-149 inhibited cell viability and promote pyroptosis, however, down-expression of miR-149 had an opposite effect in I/R treated H9C2 cells. Furthermore, miR-149 could negatively regulate FoxO3 expression by binding 3’UTR, whereas silencing of FoxO3 attenuated the effect of miR-149-mimics on cell proliferation and pyroptosis in I/R treated H9C2 cells.
CONCLUSIONS: Our study found that miR-149 played a critical role in pyroptosis during cardiac I/R injury, and thus, might provide a novel therapeutic target.
Keywords: MicroRNAs, Myocardial Contraction, Reperfusion Injury