Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
PeerJ. 2022 May 17;10:e13454. doi: 10.7717/peerj.13454. eCollection 2022.
Myasthenia gravis (MG) is an antibody-mediated autoimmune disease. In recent years, accumulating evidence has indicated that long non-coding RNAs (lncRNAs) can function as competing endogenous RNAs (ceRNAs), contributing to the progression of various autoimmune diseases. Nevertheless, the regulatory roles of ceRNAs in MG pathogenesis remain unclear. In this study, we aimed to elucidate the role of lncRNA OIP5-AS1 as a ceRNA associated with MG progression.
Real-time PCR was used to detect OIP5-AS1 levels in peripheral blood mononuclear cells (PBMCs) from patients with MG. Luciferase reporter assays were performed to validate the relationship between OIP5-AS1 and miR-181c-5p. CCK-8 and flow cytometry were performed to test the proliferation and apoptotic abilities of OIP5-AS1 in Jurkat cells. Furthermore, real-time PCR and Western blot assays were performed to explore the interactions between OIP5-AS1, miR-181c-5p, and IL-7.
The expression of OIP5-AS1 was up-regulated in patients with MG. Luciferase reporter assay indicated that OIP5-AS1 targeted the miR-181c-5p. Functional assays showed that OIP5-AS1 suppressed Jurkat cell apoptosis and promoted cell proliferation by sponging miR-181c-5p. Mechanistically, knockdown of OIP5-AS1 inhibited IL-7 expression at both the mRNA and protein levels in Jurkat cells, whereas the miR-181c-5p inhibitor blocked the reduction of IL-7 expression induced by OIP5-AS1 suppression.
We confirmed that OIP5-AS1 serves as an endogenous sponge for miR-181c-5p to regulate the expression of IL-7. Our findings provide novel insights into MG processes and suggests potential therapeutic targets for patients with MG.
重症肌无力（MG）是一种抗体介导的自身免疫性疾病。近年来，越来越多的证据表明长链非编码 RNA（lncRNA）可以作为竞争性内源 RNA（ceRNA）发挥作用，促进各种自身免疫性疾病的进展。然而，ceRNA 在 MG 发病机制中的调控作用尚不清楚。在这项研究中，我们旨在阐明 lncRNA OIP5-AS1 作为与 MG 进展相关的 ceRNA 的作用。
使用实时 PCR 检测 MG 患者外周血单个核细胞（PBMC）中的 OIP5-AS1 水平。荧光素酶报告实验验证 OIP5-AS1 与 miR-181c-5p 的关系。CCK-8 和流式细胞术检测 OIP5-AS1 在 Jurkat 细胞中的增殖和凋亡能力。此外，实时 PCR 和 Western blot 实验探讨 OIP5-AS1、miR-181c-5p 和 IL-7 之间的相互作用。
MG 患者 OIP5-AS1 表达上调。荧光素酶报告实验表明 OIP5-AS1 靶向 miR-181c-5p。功能实验表明，OIP5-AS1 通过海绵 miR-181c-5p 抑制 Jurkat 细胞凋亡并促进细胞增殖。机制上，OIP5-AS1 敲低抑制 Jurkat 细胞中 IL-7 的 mRNA 和蛋白水平表达，而 miR-181c-5p 抑制剂阻断了 OIP5-AS1 抑制引起的 IL-7 表达降低。
我们证实 OIP5-AS1 作为 miR-181c-5p 的内源性海绵来调节 IL-7 的表达。我们的研究结果为 MG 发病机制提供了新的见解，并为 MG 患者提供了潜在的治疗靶点。
