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19 November 2019 : Laboratory Research  

MiR-149 Aggravates Pyroptosis in Myocardial Ischemia-Reperfusion Damage via Silencing FoxO3

Jie Lin1ABDE*, Haihuan Lin2BCEF, Chao Ma3ABE, Fengquan Dong1ABCF, Yingchun Hu1ACF, Haiying Li1BEF

DOI: 10.12659/MSM.918410

Med Sci Monit 2019; 25:8733-8743

Abstract

BACKGROUND: 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, Cell Line, Cell Survival, Forkhead Box Protein O3, Ischemia, Myocardial Ischemia, Myocardial Reperfusion Injury, Myocytes, Cardiac, Pyroptosis, Signal Transduction

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750