Silence of LncRNA <i>GAS5</i> Protects Cardiomyocytes H9c2 against Hypoxic Injury via Sponging <i>miR</i>-<i>142</i>-<i>5p</i>.

Abstract

The regulatory role of long noncoding RNA (lncRNA) growth arrest-specific transcript 5 (<i>GAS5</i>) in both cancerous and noncancerous cells have been widely reported. This study aimed to evaluate the role of lncRNA <i>GAS5</i> in heart failure caused by myocardial infarction. We reported that silence of lncRNA <i>GAS5</i> 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 up-regulated expression of CyclinD1, CDK4 and Bcl-2. At the meantime, the expression of four heart failure-related miRNAs was altered when lncRNA <i>GAS5</i> was silenced (<i>miR-21</i> and <i>miR</i>-<i>142</i>-<i>5p</i> were up-regulated; <i>miR-30b</i> and <i>miR-93</i> were down-regulated). RNA immunoprecipitation assay results showed that lncRNA <i>GAS5</i> worked as a molecular sponge for <i>miR</i>-<i>142</i>-<i>5p</i>. More interestingly, the protective actions of lncRNA <i>GAS5</i> silence on hypoxia-stimulated cells were attenuated by <i>miR</i>-<i>142</i>-<i>5p</i> suppression. Besides, <i>TP53INP1</i> was a target gene for <i>miR</i>-<i>142</i>-<i>5p</i>. Silence of lncRNA <i>GAS5</i> promoted the activation of PI3K/AKT and MEK/ERK signaling pathways in a <i>miR</i>-<i>142</i>-<i>5p</i>-dependent manner. Collectively, this study demonstrated that silence of lncRNA <i>GAS5</i> protected H9c2 cells against hypoxia-induced injury possibly via sponging <i>miR</i>-<i>142</i>-<i>5p</i>, functionally releasing <i>TP53INP1</i> mRNA transcripts that are normally targeted by <i>miR</i>-<i>142</i>-<i>5p</i>.