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.

中文翻译：

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长链非编码 RNA SOX2-OT 通过调节 miR-27a-3p/TGFβR1 轴加剧缺氧诱导的心肌细胞损伤。

背景。心肌梗塞 (MI) 是一种由急性、持续性缺氧或缺血状况引起的严重心血管疾病。此外，心肌梗死通常会导致心力衰竭，甚至猝死。大量研究表明，长链非编码 RNA (lncRNA) 经常参与心脏病的调节。SOX2-OT 在 MI 中的具体功能和分子机制尚不清楚。研究目的。目前的研究旨在探索 SOX2-OT 在 MI 中的作用。方法. 采用生物信息学分析（DIANA 工具和 Targetscan）和广泛的实验（CCK-8、流式细胞术、RT-​​qPCR、荧光素酶报告基因、RIP、caspase-3 活性、trans-well 和蛋白质印迹分析）来研究SOX2-OT的功能和机制。结果. 我们发现缺氧处理降低了细胞活力，但增加了细胞凋亡。此外，lncRNA SOX2-OT 表达在缺氧 HCM 中上调。此后，我们证实 SOX2-OT 可以通过直接与 miR-27a-3p 结合来负调节 miR-27a-3p 的水平，并且 miR-27a-3p 也可以负调节 SOX2-OT 的水平。此外，SOX2-OT 的敲低促进了细胞增殖、迁移和侵袭，但限制了细胞凋亡。然而，这些效应被抗 miR-27a-5p 逆转。此外，我们证实 miR-27a-3p 与 TGFBR1 和 SOX2-OT 的 3'UTR 结合可调节 TGF β通过与 HCM 中的 miR-27a-3p 合作来达到 R1 水平。最终，救援试验证实 SOX2-OT 沉默或 miR-27a-3p 过表达对心肌细胞损伤过程的影响被 TGFBR1 过表达抵消。结论。长链非编码 RNA SOX2-OT 通过调节 miR-27a-3p/TGF β R1 轴加剧了缺氧诱导的心肌细胞损伤，这可能为心力衰竭的治疗提供新的见解。