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Licensed Unlicensed Requires Authentication Published by De Gruyter October 12, 2018

miR-34a-5p aggravates hypoxia-induced apoptosis by targeting ZEB1 in cardiomyocytes

  • Kaiyao Shi , Huan Sun , Hongli Zhang , Di Xie and Bo Yu EMAIL logo
From the journal Biological Chemistry

Abstract

Myocardial infarction (MI) is an unsolved health problem which seriously affects human health around the world. miR-34a-5p acting as a tumor-suppressor is associated with left ventricular remodeling. We aimed to explore the functional roles of miR-34a-5p in cardiomyocytes. Hypoxia-induced cell injury in H9c2, HL-1 and human cardiac myocytes was analyzed according to the decrease of cell viability and increase of apoptosis. Expression of miR-34a-5p was measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) when the concentration of O2 was decreased. Then, the effects of aberrantly expressed miR-34a-5p on proliferation and apoptosis of cardiomyocytes incubated under hypoxia were assessed. Finally, the downstream protein and signaling pathways of miR-34a-5p were explored. The hypoxic model was successfully constructed after incubation under hypoxia for 48 h. When the concentration of O2 decreased, the miR-34a-5p level was increased significantly. Then, we found miR-34a-5p aggravated hypoxia-induced alterations of proliferation and apoptosis in cardiomyocytes. Zinc finger E-box binding homeobox 1 (ZEB1) was identified as a target of miR-34a-5p, and miR-34a-5p conferred its function via targeting ZEB1. Finally, miR-34a-5p inhibition reversed hypoxia-induced decreases of phosphorylated kinases in the JAK/STAT and PI3K/AKT pathways through up-regulating ZEB1. Our study revealed that miR-34a-5p inhibition protected cardiomyocytes against hypoxia-induced cell injury through activating the JAK/STAT and PI3K/AKT pathways by targeting ZEB1.

  1. Conflict of interest statement: The authors declare that they have no competing interests.

  2. Funding: This study was supported by grants from the National Natural Science Foundation of China (No. 81500181).

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/hsz-2018-0195).


Received: 2018-03-21
Accepted: 2018-09-05
Published Online: 2018-10-12
Published in Print: 2019-01-28

©2019 Walter de Gruyter GmbH, Berlin/Boston

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