Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, 215008, Jiangsu, China.
Department of Gastroenterology, The North District of the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, 215008, Jiangsu, China.
Sci Rep. 2021 Jan 12;11(1):565. doi: 10.1038/s41598-020-80663-w.
Increasing evidence suggests that circular RNAs (circRNAs) play critical roles in various pathophysiological activities. However, the role of circRNAs in inflammatory bowel disease (IBD) remains unclear. Here we report the potential roles of hsa_circRNA_103765 in regulating cell apoptosis induced by TNF-α in Crohn's disease (CD). We identify that CircRNA_103765 expression was significantly upregulated in peripheral blood mononuclear cells (PBMCs) of patients with active IBD. A positive correlation with TNF-α significantly enhanced circRNA_103765 expression in CD, which was significantly reversed by anti-TNF-α mAb (infliximab) treatment. In vitro experiments showed that TNF-α could induce the expression of circRNA_103765, which was cell apoptosis dependent, while silencing of circRNA_103765 could protect human intestinal epithelial cells (IECs) from TNF-α-induced apoptosis. In addition, circRNA_103765 acted as a molecular sponge to adsorb the miR-30 family and impair the negative regulation of Delta-like ligand 4 (DLL4). Collectively, CircRNA_103765 is a novel important regulator of the pathogenesis of IBD via sponging miR-30 family-mediated DLL4 expression changes. Blockade of circRNA_103765 could serve as a novel approach for the treatment of IBD patients.
越来越多的证据表明，环状 RNA（circRNAs）在各种病理生理活动中发挥着关键作用。然而，circRNAs 在炎症性肠病（IBD）中的作用尚不清楚。在这里，我们报告了 hsa_circRNA_103765 在调节 TNF-α诱导的克罗恩病（CD）细胞凋亡中的潜在作用。我们发现，CircRNA_103765 在活动期 IBD 患者的外周血单核细胞（PBMCs）中表达显著上调。与 TNF-α的正相关显著增强了 CD 中的 circRNA_103765 表达，而抗 TNF-α mAb（英夫利昔单抗）治疗则显著逆转了这种表达。体外实验表明，TNF-α可诱导 circRNA_103765 的表达，这种表达依赖于细胞凋亡，而沉默 circRNA_103765 可保护人肠上皮细胞（IECs）免受 TNF-α诱导的凋亡。此外，circRNA_103765 作为一种分子海绵，可吸附 miR-30 家族并损害 Delta-like 配体 4（DLL4）的负调控。总之，CircRNA_103765 通过海绵吸附 miR-30 家族介导的 DLL4 表达变化，成为 IBD 发病机制的一个新的重要调节因子。阻断 circRNA_103765 可能成为治疗 IBD 患者的一种新方法。
