Department of Thoracic Surgery, Affiliated People's Hospital of Inner Mongolia Medical University.
Geriatric Medical Center, Inner Mongolia People's Hospital, Hohhot, China.
Bioengineered. 2022 Jan;13(1):280-290. doi: 10.1080/21655979.2021.2000229.
Long noncoding RNAs (lncRNAs) exert essential effects in regulating myocardial ischemia/reperfusion (MI/R)-induced injury. This work intended to explore the functions of lncRNA SOX2-OT and its regulatory mechanism within MI/R-induced injury. In this study, gene expression was determined by RT-qPCR. Western blotting was applied for the detection of protein levels. Pro-inflammatory cytokine concentrations, cardiomyocyte viability, and apoptosis were detected via ELISA, CCK-8 and flow cytometry. In the in vitro model, SOX2-OT and YY1 were both upregulated, while miR-186-5p was downregulated. SOX2-OT knockdown attenuated oxygen-glucose deprivation/reoxygenation (OGD/R)-induced cardiomyocyte dysregulation through relieving inflammation, promoting proliferation, and reducing apoptosis in OGD/R-treated H2C9 cells. SOX2-OT positively regulated YY1 expression via miR-186-5p. Moreover, miR-186-5p inhibition or YY1 upregulation abolished the effects of SOX2-OT blocking on the inflammatory responses, proliferation, and apoptosis of OGD/R-challenged H2C9 cells. In conclusion, our results, for the first time, demonstrated that SOX2-OT inhibition attenuated MI/R injury in vitro via regulating the miR-186-5p/YY1 axis, offering potential therapeutic targets for MI/R injury treatment.
长链非编码 RNA（lncRNA）在调节心肌缺血/再灌注（MI/R）损伤中发挥重要作用。本研究旨在探讨 lncRNA SOX2-OT 在 MI/R 诱导损伤中的作用及其调控机制。本研究通过 RT-qPCR 测定基因表达，Western blot 检测蛋白水平，ELISA、CCK-8 和流式细胞术检测促炎细胞因子浓度、心肌细胞活力和凋亡。在体外模型中，SOX2-OT 和 YY1 均上调，而 miR-186-5p 下调。SOX2-OT 敲低通过减轻炎症、促进增殖和减少 OGD/R 处理的 H2C9 细胞凋亡来减轻 OGD/R 诱导的心肌细胞失调。SOX2-OT 通过 miR-186-5p 正向调节 YY1 表达。此外，miR-186-5p 抑制或 YY1 上调消除了 SOX2-OT 阻断对 OGD/R 挑战的 H2C9 细胞炎症反应、增殖和凋亡的影响。总之，我们的研究结果首次表明，SOX2-OT 抑制通过调节 miR-186-5p/YY1 轴来减轻体外 MI/R 损伤，为 MI/R 损伤治疗提供了潜在的治疗靶点。
