GAS5 silencing attenuates hypoxia‐induced cardiomyocytes injury by targeting miR‐21/PTEN

Abstract

Introduction Myocardial hypoxia is an important factor causing myocardial infarction (MI). Interestingly, many unknown factors in the molecular mechanism of MI remain unclear. Our study explored the role of lncRNA growth arrest‐specific 5 (GAS5) in cell injury under hypoxia. Methods AS5 expression was assessed in MI and human cardiomyocytes under hypoxia through RT‐qPCR assay. Methyl thiazolyl tetrazolium assay, flow cytometry assay, and transwell assay was carried out for cell viability, cell apoptosis, cell migration, and invasion, respectively. The regulatory target of GAS5 was explored through a dual‐luciferase reporter assay. Results Our findings indicated that the upregulation of GAS5 was related to hypoxia. Downregulation of GAS5 expression could decrease hypoxia‐induced cell apoptosis and increase cell migration and invasion. Moreover, GAS 5 targeted miR‐21, which regulated the phosphatase and tension homology deleted on chromosome ten gene (PTEN) expression. Furthermore, the knockdown of miR‐21 eliminated the effect of GAS5 silencing on cell injury. Conclusion These results indicated that lncRNA GAS5 silencing decreased cardiomyocyte injury by hypoxia‐induced through regulating miR‐21/PTEN.

Long Non-Coding RNAs (lncRNAs) in Heart Failure: A Comprehensive Review

“…These regulatory roles of lncRNAs have important implications for the development and progression of HF [ 50 ]. For example, antisense lncRNA Kcna2 (Long non-coding RNA Potassium Voltage-Gated Channel Subfamily A Member 2) is linked to a higher prevalence of ventricular arrhythmias, which are irregular heartbeats that only impact the heart’s lower chambers in heart failure patients [ 51 ]. The study found that Kcna2 knockdown in the heart decreased the slow component of the rectifier potassium current (IKs) and prolonged action potentials in cardiomyocytes, consistent with the changes observed in heart failure.…”

“…Conversely, Kcna2 overexpression in the heart significantly attenuated the CHF-induced decreases in the IKs, AP prolongation, and ventricular arrhythmias. This discovery highlights the role of lncRNAs in cardiac electrical remodeling and the development of arrhythmias in heart failure [ 51 ]. Additionally, lncRNA UCA1 (Long non-coding RNA urothelial carcinoma-associated 1) has been shown to promote the progression of cardiac hypertrophy, a condition commonly associated with various cardiovascular diseases such as heart failure.…”

“…It is a small nucleolar RNA host gene, containing multiple C/D box snoRNA genes in its introns. The secondary RNA structure of the encoded transcript mimics glucocorticoid response element (GRE), which means it can bind to the DNA binding domain of the glucocorticoid receptor (GR) and block its activation, thereby stopping it from regulating the transcription of its target genes [ 51 ]. GAS5 has been linked to apoptosis and cellular growth arrest.…”

“…However, the specific role of GAS5 in heart failure is yet to be determined. To study the same, a study was conducted by Wang and Xie [ 51 ] that aimed to evaluate the importance and its role in heart failure development post-myocardial infarction of lncRNA GAS5 in hypoxia-injured H9c2 cells, which is a type of cardiac muscle cell line that was derived from embryonic rat hearts. The results of this study demonstrated that lncRNA GAS5 was significantly upregulated in hypoxia-injured H9c2 cells and its expression inhibited the progression of heart failure caused by myocardial infarction [ 51 ].…”

“…To study the same, a study was conducted by Wang and Xie [ 51 ] that aimed to evaluate the importance and its role in heart failure development post-myocardial infarction of lncRNA GAS5 in hypoxia-injured H9c2 cells, which is a type of cardiac muscle cell line that was derived from embryonic rat hearts. The results of this study demonstrated that lncRNA GAS5 was significantly upregulated in hypoxia-injured H9c2 cells and its expression inhibited the progression of heart failure caused by myocardial infarction [ 51 ]. It is also known that LncRNAs take part in interactions with several major regulators that are involved in the modulation of calcium ions, such as zinc finger antisense 1 (ZFAS1), myocardial infarction-associated transcript (Miat), and zinc finger protein antisense RNA (ZNF593-AS) [ 54 , 55 ].…”