CircRNA malignant fibrous histiocytoma amplified Sequence 1 (MFHAS1) reduced inflammatory responses in a Colitis Model via SIRT1/NF-κB

Abstract Ulcerative colitis (UC) is a chronic and non-specific inflammatory bowel disease (IBD). Its pathogenesis remains unclear, but its morbidity shows an increasing trend year by year. The pathogenesis of UC may be related to the genetic susceptibility, immune factor and intestinal microflora. In the last few years, an increasing number of studies have examined the relationship between the expression levels of peripheral CircRNA and UC. We aimed to evaluate the efficacy of CircRNA MFHAS1 in colitis and its possible mechanism. The expression of CircRNA MFHAS1 was reduced in colitis, and miR-486-5p expression was also increased in citrobacter rodentium-induced murine colitis. In vitro model, over-expression of CircRNA MFHAS1 reduced inflammatory responses, induced SIRT1 protein expression, and suppressed NF-κB protein expression. However, miR-486-5p CircRNA MFHAS1 suppressed SIRT1 protein expression, and induced NF-κB protein expression in vitro model. The inactivation of SIRT1 reduced the anti-inflammation effects of CircRNA MFHAS1 on inflammatory responses in vitro model. Over-expression of miR-486-5p also reduced the anti-inflammation effects of CircRNA MFHAS1 in vitro model. Our results demonstrated that CircRNA MFHAS1 reduces inflammatory responses in Colitis via SIRT1/NF-κB by miR-486-5p.

摘要 溃疡性结肠炎（Ulcerative colitis, UC）是一种慢性非特异性炎症性肠病（Inflammatory bowel disease, IBD）。其发病机制尚未完全阐明，但发病率呈逐年上升趋势。UC的发病机制可能与遗传易感性、免疫因素及肠道菌群相关。近年来，越来越多的研究探讨了外周血环状RNA（CircRNA）表达水平与UC之间的关联。本研究旨在评估环状RNA MFHAS1（CircRNA MFHAS1）在结肠炎中的作用及其潜在机制。在啮齿枸橼酸杆菌诱导的小鼠结肠炎模型中，CircRNA MFHAS1的表达水平降低，而miR-486-5p的表达水平升高。体外实验模型中，过表达CircRNA MFHAS1可减轻炎症反应，上调沉默信息调节因子1（SIRT1）蛋白表达，并抑制核因子κB（NF-κB）蛋白表达。然而，在体外模型中共转染miR-486-5p与CircRNA MFHAS1后，CircRNA MFHAS1对SIRT1蛋白表达的上调作用被抑制，且可促进NF-κB蛋白表达。体外实验中，SIRT1的失活可削弱CircRNA MFHAS1的抗炎作用。过表达miR-486-5p同样可削弱CircRNA MFHAS1的抗炎效果。本研究结果表明，CircRNA MFHAS1可通过miR-486-5p介导的SIRT1/NF-κB通路减轻结肠炎的炎症反应。