title: Downregulation of miR-122 attenuates hypoxia/reoxygenation (H/R)-induced myocardial cell apoptosis by upregulating GATA-4.
abstract: 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 miR-122 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 miR-122 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.
authors: The Third Department of Cardiovascular Medicine, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453100, China. Electronic address: wanqianliangwql@163.com.
authors: Wanqian
authors: W
authors: Liang
authors: The Second Department of Cardiovascular Medicine, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453100, China.
authors: Junxia
authors: J
authors: Guo
authors: The Third Department of Cardiovascular Medicine, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453100, China.
authors: Jianhua
authors: J
authors: Li
authors: The Third Department of Cardiovascular Medicine, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453100, China.
authors: Caiyan
authors: C
authors: Bai
authors: Neonatal Intensive Care Unit, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453100, China.
authors: Yuan
authors: Y
authors: Dong
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D001483:Base Sequence; D015687:Cell Hypoxia / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D015536:Down-Regulation / Q000187:drug effects* / Q000235:genetics; D050991:GATA4 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D010100:Oxygen / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics*
chemical_list: D050991:GATA4 Transcription Factor; C580643:MIRN122 microRNA, rat; D035683:MicroRNAs; D012333:RNA, Messenger; D010100:Oxygen
keywords: Apoptosis; GATA-4; Hypoxia/reoxygenation; Myocardial cell; miR-122