Hsa-miR-10a-5p/RNF186 modulates endoplasmic reticulum stress to exacerbate the development of ulcerative colitis.

Abstract

Ulcerative colitis (UC) is a chronic inflammatory bowel disease, and endoplasmic reticulum stress (ERS) may contribute to the pathogenesis and progression of UC. Previous research has found that hsa-miR-10a-5p is abnormally expressed in UC, but its molecular mechanisms remain unclear. This study aimed to explore the role of hsa-miR-10a-5p in regulating ERS in UC through RNF186. LPS-induced HT-29 cells and a dextran sulfate sodium (DSS)-induced animal model were utilized to explore the regulatory roles of hsa-miR-10a-5p and RNF186 in ERS in UC. Following modulation of hsa-miR-10a-5p and RNF186 expression, we assessed the expression of ERS-related genes in the UC model using qPCR and immunofluorescence, and evaluated apoptosis with flow cytometry and WB. Furthermore, we conducted DAI scoring, HE staining, and permeability testing in the animal model, and analyzed the inflammatory profile of UC by ELISA to further understand disease progression and the impact of molecular changes on intestinal pathology. Overexpression of hsa-miR-10a-5p in HT-29 cells and animal models promoted cell proliferation, inhibited apoptosis, and mitigated inflammatory factor release and ERS response. Conversely, miR-10a-5p knockdown activated colonic mucosal epithelial damage, reduced cell proliferation, increased apoptosis, aggravated ERS response, and enhanced inflammatory factor expression. This research elucidated that hsa-miR-10a-5p participates in the process of UC development and progression by modulating the ERS response through RNF186. This discovery offered novel insights, enhancing our comprehension of the underlying pathophysiology of UC and provided a theoretical basis for the potential application of miRNAs in UC therapy.