Downregulation of miR-122 attenuates hypoxia/reoxygenation (H/R)-induced myocardial cell apoptosis by upregulating GATA-4

作者：Liang, Wanqian^*; Guo, Junxia; Li, Jianhua; Bai, Caiyan; Dong, Yuan

来源：Biochemical and Biophysical Research Communications, 2016, 478(3): 1416-1422.

DOI：10.1016/j.bbrc.2016.08.139

• miR-122
• Hypoxia/reoxygenation
• Myocardial cell
• Apoptosis
• GATA-4

MicroRNA-122 has been reported to play a potential role in the apoptosis of myocardial cells. However, the effect of miR-122 in regulating myocardial ischemic injury has not been previously addressed. This study aimed to investigate the effect and the molecular basis of miR-122 on myocardial ischemic injury. Using the hypoxia/reoxygenation (H/R) model of rat cardiomyocytes H9C2 in vitro, we found that miR122 was highly expressed in H9C2 cells after H/R treatment. Overexpression of miR-122 by recombinant adeno-associated viral vector infection markedly promoted the apoptosis of H9C2 cells induced by H/R treatment, whereas miR-122 inhibition significantly decreased cell apoptosis. Dual-luciferase reporter assay and western blot assay revealed that GATA-4 was a direct target gene of miR-122, and miR122 suppressed the expression of GATA-4 via binding to its 3'-UTR. We further identified that overexpression of miR-122 inhibited the expression of GATA-4 at the mRNA and protein levels, whereas the inhibition of miR-122 upregulated the expression of GATA-4. Moreover, GATA-4 was poorly expressed in H/R H9C2 cells and the apoptosis induced by H/R was associated with the decrease in GATA-4 expression. Importantly, silencing of GATA-4 apparently abrogated the inhibitory effect of anti-miR-122 on H/R-induced cell apoptosis. In conclusion, these findings indicate that downregulation of miR-122 alleviates cardiomyocyte H/R injury through upregulation of GATA-4 expression, supplying a novel molecular target for myocardial ischemic injury.

• 出版日期2016-9-23
• 单位新乡医学院