Circular RNA HECTD1 Mitigates Ulcerative Colitis by Promoting Enterocyte Autophagy Via miR-182-5p/HuR Axis
Circular RNA HECTD1 Mitigates Ulcerative Colitis by Promoting Enterocyte Autophagy Via miR-182-5p/HuR Axis
复制标题
环状 RNA HECTD1 通过 miR-182-5p/HuR 轴促进肠细胞自噬来减轻溃疡性结肠炎。
DOI：
10.1093/ibd/izab188
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发表时间：
2021-08-24
影响因子：
4.9
通讯作者：
Ouyang, Miao
中科院分区：
文献类型：
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作者：
Xu, Yan;Tian, Yuxi;Ouyang, Miao
目的溃疡性结肠炎（UC）是一种病因不明的慢性结肠炎。Circular RNA（circRNA）在许多疾病中显示出调节作用，但circRNA在UC中的作用尚不清楚。本研究旨在揭示circRNA HECTD 1（circHECTD 1）在UC中的功能及其调控机制。方法收集60例活动期UC患者和30例健康对照者的结肠黏膜组织进行H&E染色。使用脂多糖（LPS）和葡聚糖硫酸钠（DSS）在Caco-2细胞和C57 BL/6小鼠中诱导炎症和UC，其中发生circHECTD 1、miR-182- 5 p和/或人抗原R（HuR）的修饰。收集DSS处理的小鼠的Caco-2细胞和结肠组织用于分析炎性细胞因子、NLRP 3炎性体和自噬相关蛋白的表达水平。验证了circHECTD 1、miR-182- 5 p和HuR之间的相互作用。结果UC患者结肠黏膜组织自噬功能受损，circHECTD 1和HuR表达降低。过表达circHECTD 1或HuR或抑制miR-182- 5 p抑制炎症并促进LPS诱导的Caco-2细胞的自噬。circHECTD 1通过miR-182- 5 p促进Caco-2细胞中HuR的表达。circHECTD 1的过表达通过促进DSS治疗小鼠的自噬来减少结肠损伤和炎症。结论circHECTD 1过表达可通过miR-182- 5 p促进HuR依赖性自噬而减轻UC。这项研究强调了circHECTD 1对UC的治疗潜力，并增加了circRNA在UC发病机制中的知识。
Objective Ulcerative colitis (UC) is a chronic colitis with unknown etiology. Circular RNA (circRNA) has shown regulatory effect in many diseases, but the role of circRNA in UC is barely known. This study uncovers the function and regulatory mechanism of circRNA HECTD1 (circHECTD1) in UC. Methods Colonic mucosal tissues of 60 patients with active UC and 30 healthy controls were collected for H&E staining. Lipopolysaccharide (LPS) and dextran sulfate sodium (DSS) were used to induce inflammation and UC in Caco-2 cells and C57BL/6 mice where modification of circHECTD1, miR-182-5p and/or human antigen R (HuR) took place. The Caco-2 cells and the colon tissues of DSS-treated mice were collected for analysis of the expression levels of inflammatory cytokines, NLRP3 inflammasome, and autophagy-related proteins. The interactions among circHECTD1, miR-182-5p, and HuR were verified. Results The colonic mucosal tissues of UC patients showed impaired autophagy and decreased expressions of circHECTD1 and HuR. Overexpression of circHECTD1 or HuR or inhibition of miR-182-5p suppressed inflammation and promoted autophagy of LPS-induced Caco-2 cells. The expression of HuR was promoted by circHECTD1 via miR-182-5p in Caco-2 cells. Overexpression of circHECTD1 reduced colonic injuries and inflammation by promoting autophagy in DSS-treated mice. Conclusion Overexpression of circHECTD1 alleviates UC by promoting HuR-dependent autophagy via miR-182-5p. This study highlights the therapeutic potential of circHECTD1 for UC and adds to the knowledge of circRNA in the pathogenesis of UC.