Journal of Inflammation Research (May 2021)
MiRNA-29c-3p Promotes Intestinal Inflammation via Targeting Leukemia Inhibitory Factor in Ulcerative Colitis
Abstract
Jian Guo,1,2 Ruiya Zhang,3 Yiqing Zhao,3 Junping Wang3 1Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, Taiyuan, 030006, People’s Republic of China; 2Department of General Surgery, Shanxi Provincial People’s Hospital, The Affiliated People’s Hospital of Shanxi Medical University, Taiyuan, 030012, People’s Republic of China; 3Department of Gastroenterology, Shanxi Provincial People’s Hospital, The Affiliated People’s Hospital of Shanxi Medical University, Taiyuan, Shanxi, 030012, People’s Republic of ChinaCorrespondence: Junping WangDepartment of Gastroenterology, Shanxi Provincial People’s Hospital, The Affiliated People’s Hospital of Shanxi Medical University, 29 Shuangtasi Road, Taiyuan, Shanxi, 030012, People’s Republic of ChinaTel + 351-4960130Email [email protected]: Dysregulation of micro-RNAs (miRNAs) is profoundly linked to inflammatory bowel diseases (IBD), but little is known about the specific biological functions of miRNAs in IBD. This study sought to elucidate the effect and the underlying target of miR-29c-3p in ulcerative colitis (UC).Methods: The levels of miR-29c-3p and leukemia inhibitory factor (LIF) were measured in inflamed lesions of UC patients and dextran sulfate sodium (DSS)-induced colitis mice by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. MiR-29c-3p was predicted to target LIF by bioinformatics software, which was verified via luciferase reporter assay and transfection of miR-29c-3p mimics or inhibitor. The role of miR-29c-3p/LIF axis in intestinal inflammation was explored in experimental colitis mice and Caco-2 cells.Results: MiR-29c-3p was markedly downregulated while LIF was upregulated in colon tissues of UC patients and DSS-challenged colitis mice as well as in primary intestinal epithelial cells (IECs) and LPS-treated Caco-2 cells. MiR-29c-3p inhibited LIF expression at the transcriptional level via binding to LIF 3ʹ-untranslated region (UTR) in Caco-2 cells. Targeting miR-29c-3p/LIF axis regulated inflammatory cytokines production, cell proliferation and apoptosis. Overexpression of miR-29c-3p aggravated mice experimental colitis via suppressing LIF.Conclusion: Our findings demonstrate that the upregulation of miR-29c-3p promotes gut inflammation and the expression of pro-inflammatory mediators via suppressing LIF, thereby modulating the pathogenesis of UC.Keywords: ulcerative colitis, microRNA-29c-3p, leukemia inhibitory factor, inflammation, apoptosis
