OBJECTIVES Ischemic heart failure (IHF) is the most common cause of death globally. Growing evidence shows abnormal expression of long non-coding RNAs in heart failure patients. This study aims to investigate the effect of sex-determining region Y-box 2 (SOX2) overlapping transcript (SOX2-OT) on the regulation of the inflammatory response in ischemic heart failure. METHODS IHF rat and oxygen and glucose deprivation (OGD) cell models were established. qRT-PCR was employed to investigate the expression of SOX2-OT. ELISA, western blot and cell viability/apoptosis assays were performed to assess the effects of SOX2-OT. Online software program was used to identify miRNAs that target SOX2-OT, followed by validation using RNA pull-down. Potential targets of miRNAs were searched, and examined by immunoblotting, qRT-PCR and luciferase reporter assay. RESULTS SOX2-OT was up-regulated in IHF and OGD. Knockdown of SOX2-OT promoted cell proliferation, decreased apoptosis rate and cell oxidative damage, and ameliorated inflammatory response. SOX2-OT contains binding sites for miR-455-3p, miR-5586-3p and miR-1252-5p. RNA pull-down confirmed the binding ability between SOX2-OT and miR-455-3p. TRAF6 is a direct target of miR-455-3p. Moreover, the regulatory activity of SOX2-OT on inflammatory response was partially through its negative regulation of miR-455-3p, which directly regulates TRAF6. Down-regulation of SOX2-OT improved myocardial dysfunction in IHF rat. CONCLUSIONS Our results reveal that SOX2-OT may be a driver of IHF through repression of miR-455-3p, and miR-455-3p alleviates IHF by targeting TRAF6. Therefore, SOX2-OT/miR-455-3p/TRAF6 may be a potential target for advanced therapeutic strategy for IHF.

中文翻译：

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LncRNA通过调节miR-455-3p / TRAF6轴促进缺血性心力衰竭的炎症反应。

目的缺血性心力衰竭（IHF）是全球最常见的死亡原因。越来越多的证据表明，心力衰竭患者中长非编码RNA的异常表达。本研究旨在研究性别决定区域Y-box 2（SOX2）重叠转录本（SOX2-OT）对缺血性心力衰竭中炎症反应的调节作用。方法建立IHF大鼠和缺氧缺糖（OGD）细胞模型。采用qRT-PCR研究SOX2-OT的表达。进行了ELISA，蛋白质印迹和细胞活力/凋亡测定以评估SOX2-OT的作用。在线软件程序用于识别靶向SOX2-OT的miRNA，然后使用RNA下拉进行验证。搜索了miRNA的潜在靶标，并通过免疫印迹，qRT-PCR和荧​​光素酶报告基因检测进行了检查。结果SOX2-OT在IHF和OGD中上调。降低SOX2-OT促进细胞增殖，降低细胞凋亡率和细胞氧化损伤，并改善炎症反应。SOX2-OT包含miR-455-3p，miR-5586-3p和miR-1252-5p的结合位点。RNA下拉证实了SOX2-OT与miR-455-3p之间的结合能力。TRAF6是miR-455-3p的直接靶标。此外，SOX2-OT对炎症反应的调节活性部分是通过其对miR-455-3p的负调节而直接调节TRAF6。SOX2-OT的下调改善了IHF大鼠的心肌功能障碍。结论我们的结果表明SOX2-OT可能是通过抑制miR-455-3p来促进IHF的，而miR-455-3p可以通过靶向TRAF6减轻IHF。因此，