Department of Emergency, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China.
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China.
BMC Cardiovasc Disord. 2024 May 30;24(1):286. doi: 10.1186/s12872-024-03954-4.
Septic cardiomyopathy is one of the most severe and common complications in patients with sepsis and poses a great threat to their prognosis. However, the potential mechanisms and effective therapeutic drugs need to be explored. The control of cardiac cell death by miRNAs has emerged as a prominent area of scientific interest in the diagnosis and treatment of heart disorders in recent times. In the present investigation, we discovered that overexpression of miR-31-5p prevented LPS-induced damage to H9C2 cells and that miR-31-5p could inhibit BAP1 production by binding to its 3'-UTR. BRCA1-Associated Protein 1 (BAP1) is a ubiquitin carboxy-terminal hydrolase. BAP1 upregulation blocked effect of miR-31-5p on H9C2 cell injury. Moreover, BAP1 inhibited the expression of solute carrier family 7 member 11 (SLC7A11) by deubiquitinating histone 2 A (H2Aub) on the promoter of SLC7A11. Furthermore, overexpression of miR-31-5p and downregulation of BAP1 inhibited SLC7A11 mediated ferroptosis. In addition, the downregulation of SLC7A11 reversed the inhibitory effect of miR-31-5p on the expression of myocardial injury and inflammatory factors, and cell apoptosis was reversed. In conclusion, these results indicate that miR-31-5p alleviates malignant development of LPS-induced H9C2 cell injury by targeting BAP1 and regulating SLC7A11 deubiquitination-mediated ferroptosis, which confirmed the protective effect of miR-31-5p on H9C2 cell injury and revealed potential mechanisms that may provide new targets for treatment of septic cardiomyopathy.
脓毒症性心肌病是脓毒症患者最严重和最常见的并发症之一，对其预后构成极大威胁。然而，其潜在机制和有效治疗药物仍需探索。近年来，miRNA 控制心脏细胞死亡在心脏疾病的诊断和治疗中成为一个备受关注的领域。在本研究中，我们发现 miR-31-5p 的过表达可防止 LPS 诱导的 H9C2 细胞损伤，miR-31-5p 可通过结合其 3'UTR 抑制 BAP1 的产生。BRCA1 相关蛋白 1（BAP1）是一种泛素羧基末端水解酶。BAP1 的上调阻断了 miR-31-5p 对 H9C2 细胞损伤的作用。此外，BAP1 通过去泛素化组蛋白 2A（H2Aub）抑制 SLC7A11 启动子上的 solute carrier family 7 member 11（SLC7A11）的表达。此外，miR-31-5p 的过表达和 BAP1 的下调抑制了 SLC7A11 介导的铁死亡。此外，下调 SLC7A11 逆转了 miR-31-5p 对心肌损伤和炎症因子表达的抑制作用，细胞凋亡也得到逆转。综上所述，这些结果表明，miR-31-5p 通过靶向 BAP1 调节 SLC7A11 去泛素化介导的铁死亡来减轻 LPS 诱导的 H9C2 细胞损伤的恶性发展，证实了 miR-31-5p 对 H9C2 细胞损伤的保护作用，并揭示了可能为脓毒症性心肌病治疗提供新靶点的潜在机制。
