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J Cell Biochem. 2019 Mar 19. doi: 10.1002/jcb.28596. [Epub ahead of print]

STAT1-avtiviated LINC00961 regulates myocardial infarction by the PI3K/AKT/GSK3β signaling pathway.

Liu S1,2, He Y3, Shi J1, Liu L1, Ma H1, He L1, Guo Y1.

Author information

1
Department of Cardiovascular Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
2
Cardiac Surgery Center, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan, China.
3
Psychosomatic Medicine Center, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, China.

Abstract

Myocardial infarction (MI) remains a severe cardiac disease because of its high incidence and mortality worldwide. A growing body of recent investigations have confirmed that LINC00961 acts as a tumor suppressor in diverse malignancies. However, the biological significance of LINC00961 and its molecular mechanism in MI are still elusive. Hypoxia is the leading cause of MI and induces myocardial injury. In this study, we found the upregulated expression of LINC00961 in cardiomyocytes H9c2 after hypoxia treatment. Knockdown of LINC00961 ameliorated hypoxia-induced cell injury by facilitating cell viability while repressing cell apoptosis. The significant increase of signal transducer and activator of transcription 1 (STAT1) expression and phosphorylation levels was observed in hypoxia-induced cells and proved to exacerbate hypoxia injury. In addition, STAT1 transcriptionally activated LINC00961 by binding to LINC00961 promoter. Furthermore, our results validated that suppressing LINC00961 contributed to the remarkable diminution in the phosphorylation levels of phosphoinositide 3-kinases (PI3K), AKT, and glycogen synthase kinase-3β (GSK3β). Inhibition of PI3K/AKT signaling or GSK3β pathway rescued the effects of LINC00961 knockdown on the hypoxia-induced injury of cardiomyocytes. Namely, we concluded that STAT1-avtiviated LINC00961 accelerated MI via the PI3K/AKT/GSK3β pathway, which may provide clues for the treatment of patients with MI.

KEYWORDS:

LINC00961; long noncoding RNA; myocardial infarction (MI); phosphoinositide 3-kinases (PI3K); signal transducer and activator of transcription 1 (STAT1)

PMID:
30887575
DOI:
10.1002/jcb.28596

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