Long Noncoding RNA SOX2-OT Exacerbates Hypoxia-Induced Cardiomyocytes Injury by Regulating miR-27a-3p/TGFβR1 Axis

Abstract

Background. Myocardial infarction (MI) was a severe cardiovascular disease resulted from acute, persistent hypoxia, or ischemia condition. Additionally, MI generally led to heart failure, even sudden death. A multitude of research studies proposed that long noncoding RNAs (lncRNAs) frequently participated in the regulation of heart diseases. The specific function and molecular mechanism of SOX2-OT in MI remained unclear. Aim of the Study. The current research was aimed to explore the role of SOX2-OT in MI. Methods. Bioinformatics analysis (DIANA tools and Targetscan) and a wide range of experiments (CCK-8, flow cytometry, RT-qPCR, luciferase reporter, RIP, caspase-3 activity, trans-well, and western blot assays) were adopted to investigate the function and mechanism of SOX2-OT. Results. We discovered that hypoxia treatment decreased cell viability but increased cell apoptosis. Besides, lncRNA SOX2-OT expression was upregulated in hypoxic HCMs. Hereafter, we confirmed that SOX2-OT could negatively regulate miR-27a-3p levels by directly binding with miR-27a-3p, and miR-27a-3p also could negatively regulate SOX2-OT levels. Furthermore, knockdown of SOX2-OT promoted cell proliferation, migration, and invasion, but limited cell apoptosis. However, these effects were reversed by anti-miR-27a-5p. Besides, we verified that miR-27a-3p binding with the 3′UTR of TGFBR1 and SOX2-OT regulated TGFβR1 level by collaborating with miR-27a-3p in HCMs. Eventually, rescue assays validated that the influence of SOX2-OT silence or miR-27a-3p overexpression on cellular processes in cardiomyocytes injury was counteracted by TGFBR1 overexpression. Conclusions. Long noncoding RNA SOX2-OT exacerbated hypoxia-induced cardiomyocytes injury by regulating miR-27a-3p/TGFβR1 axis, which may provide a novel insight for heart failure treatment.

RETRACTED ARTICLE: LncRNA SOX2-OTinhibitionprotects against myocardialischemia/reperfusion-inducedinjury via themicroRNA-186-5p (miR-186-5p)/Yin Yang 1 (YY1)pathway

“…To cite an instance, Gu et al elaborated that SOX2-OT facilitated inflammation and apoptosis in ischemic heart failure by regulating TRAF6 via miR-455-3p [ 25 ]. As elucidated in a report from Yang et al, SOX2-OT aggravated myocardial infarction through the miR-27a-3p/TGFBR1 pathway [ 28 ]. Similarly, Tu et al found that SOX2-OT exacerbated ischemia-induced heart failure in a murine model [ 29 ].…”

LncRNA HOTTIP Knockdown Attenuates Acute Myocardial Infarction via Regulating miR-92a-2/c-Met Axis

“…LncRNA XIST upregulation effectively inhibits hypoxia-induced cardiomyocyte apoptosis by targeting miR-150-5p/Bax axis during AMI progression [ 40 ]. In addition, lncRNAs SOX2-OT [ 41 ], RMRP [ 42 ], HULC [ 43 ] and MHRT [ 44 ] are also involved in regulating hypoxia-treated cardiomyocyte apoptosis. Although lncRNA HOTTIP has been identified to play crucial roles in coronary artery diseases, its effect and specific mechanism in AMI have not been reported.…”

Identification of Two Long Non-Coding RNAs AC010082.1 and AC011443.1 as Biomarkers of Coronary Heart Disease Based on Logistic Stepwise Regression Prediction Model

“…TGFBR3 expression is significantly upregulated in patients after myocardial infarction and may serve as a therapeutic target and biomarker for myocardial damage by activating p38 MAPK to induce cardiomyocyte apoptosis ( Chu et al, 2011 ; Chen et al, 2019 ). Moreover, it has been found that lncRNA SOX2-OT exacerbates hypoxia-induced cardiomyocyte injury by regulating the miR-27a-3p/TGFβR1 axis ( Yang and Lin, 2020 ). Therefore, we speculated that AC010082.1 and AC011443.1 play important roles in the pathological progression of CHD through the ceRNA mechanism and are potential biomarkers of CHD.…”