Department of Intensive Care Unit, Wuxi Second People's Hospital, Wuxi, 214000 Jiangsu, China.
Cardiovasc Ther. 2022 May 31;2022:7332298. doi: 10.1155/2022/7332298. eCollection 2022.
Reperfusion therapy, the standard treatment for acute myocardial infarction (MI), can trigger necrotic death of cardiomyocytes and provoke ischemia/reperfusion (I/R) injury. However, molecular mechanisms that regulate cardiomyocyte death remain largely unknown. The abnormal expression of lncRNA MIR22HG has been found in types of diseases. The current study was aimed at exploring the function and mechanism of MIR22HG in I/R injury. In this study, mouse myocardial cells (HL-1) treated with oxygen-glucose deprivation and reoxygenation (OGD/R) were used as the models, and myocardial ischemia reperfusion injury (MIRI) animal models were established in male C57BL/6 mice. Experiments including CCK-8, flow cytometry, TUNEL, HE staining, RT-qPCR, western blotting, and luciferase reporter assays were performed to explore the function and potential mechanism of MIR22HG in MIRI and . Bioinformatics analysis was performed to predict the binding site between miR-9-3p and MIR22HG (or SH2B3). Our results indicated that the MIR22HG level was upregulated in cardiomyocytes after OGD/R treatment. The knockdown of MIR22HG promoted cell viability and inhibited apoptosis and extracellular matrix (ECM) production in OGD/R-treated HL-1 cells. In mechanism, MIR22HG binds to miR-9-3p, and miR-9-3p targets the SH2B3 3' untranslated region (UTR). Moreover, SH2B3 expression was positively regulated by MIR22HG but negatively modulated by miR-9-3p. Rescue assays suggested that the suppressive effect of MIR22HG knockdown on cell viability, apoptosis, and ECM accumulation was reversed by the overexpression of SH2B3. The experiments demonstrated that MIR22HG knockdown alleviated cardiomyocyte apoptosis and reduced myocardial infarct size in MIRI mice. In summary, MIR22HG knockdown alleviates myocardial injury through the miR-9-3p/SH2B3 axis.
再灌注治疗是急性心肌梗死（MI）的标准治疗方法，它可以触发心肌细胞的坏死性死亡，并引发缺血/再灌注（I/R）损伤。然而，调节心肌细胞死亡的分子机制在很大程度上尚不清楚。异常表达的 lncRNA MIR22HG 已在多种疾病中被发现。本研究旨在探讨 MIR22HG 在 I/R 损伤中的作用和机制。在这项研究中，使用氧葡萄糖剥夺和再氧合（OGD/R）处理的小鼠心肌细胞（HL-1）作为模型，并在雄性 C57BL/6 小鼠中建立心肌缺血再灌注损伤（MIRI）动物模型。进行了包括 CCK-8、流式细胞术、TUNEL、HE 染色、RT-qPCR、western blotting 和荧光素酶报告基因测定在内的实验，以探讨 MIR22HG 在 MIRI 中的功能和潜在机制。进行了生物信息学分析，以预测 miR-9-3p 和 MIR22HG（或 SH2B3）之间的结合位点。我们的结果表明，OGD/R 处理后心肌细胞中 MIR22HG 水平上调。MIR22HG 的敲低可促进 OGD/R 处理的 HL-1 细胞中的细胞活力，并抑制细胞凋亡和细胞外基质（ECM）产生。在机制上，MIR22HG 与 miR-9-3p 结合，而 miR-9-3p 靶向 SH2B3 的 3'非翻译区（UTR）。此外，SH2B3 的表达受 MIR22HG 的正调控，受 miR-9-3p 的负调控。挽救实验表明，SH2B3 的过表达逆转了 MIR22HG 敲低对细胞活力、凋亡和 ECM 积累的抑制作用。体内实验表明，MIR22HG 敲低可减轻 MIRI 小鼠的心肌细胞凋亡并减少心肌梗死面积。总之，MIR22HG 敲低通过 miR-9-3p/SH2B3 轴减轻心肌损伤。
