Mol. Cells 2019; 42(3): 245  https://doi.org/10.14348/molcells.2018.0180
Silence of LncRNA GAS5 Protects Cardiomyocytes H9c2 Against Hypoxic Injury via Sponging miR-142-5p
Jian Du, Si-Tong Yang, Jia Liu, Ke-Xin Zhang, and Ji-Yan Leng*
Department of Cadre Ward, The First Hospital of Jilin University, Changchun, Jilin 130021, China
Received April 24, 2018; Revised September 6, 2018; Accepted October 2, 2018.; Published online April 15, 2019.
© Korean Society for Molecular and Cellular Biology. All rights reserved.

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit (http://creativecommons.org/licenses/by-nc-sa/3.0/).
ABSTRACT
The regulatory role of long noncoding RNA (lncRNA) growth arrest specific transcript 5 (GAS5) in both cancerous and noncancerous cells have been widely reported. This study aimed to evaluate the role of lncRNA GAS5 in heart failure caused by myocardial infarction. We reported that silence of lncRNA GAS5 attenuated hypoxia-triggered cell death, as cell viability was increased and apoptosis rate was decreased. This phenomenon was coupled with the down-regulated expression of p53, Bax and cleaved caspase-3, as well as the upregulated expression of CyclinD1, CDK4 and Bcl-2. At the meantime, the expression of four heart failure-related miRNAs was altered when lncRNA GAS5 was silenced (miR-21 and miR-142-5p were up-regulated; miR-30b and miR-93 were down-regulated). RNA immunoprecipitation assay results showed that lncRNA GAS5 worked as a molecular sponge for miR-142-5p . More interestingly, the protective actions of lncRNA GAS5 silence on hypoxia-stimulated cells were attenuated by miR-142-5p suppression. Besides, TP53INP1 was a target gene for miR-142-5p . Silence of lncRNA GAS5 promoted the activation of PI3K/AKT and MEK/ERK signaling pathways in a miR-142-5p -dependent manner. Collectively, this study demonstrated that silence of lncRNA GAS5 protected H9c2 cells against hypoxia-induced injury possibly via sponging miR-142-5p , functionally releasing TP53INP1 mRNA transcripts that are normally targeted by miR-142-5p.
Keywords: H9c2 cell, heart failure, hypoxia, lncRNA GAS5 ,miR-142-5p


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