LncRNA TUG1 regulates the balance of HuR and miR-29b-3p and inhibits intestinal epithelial cell apoptosis in a mouse mod
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RESEARCH ARTICLE
LncRNA TUG1 regulates the balance of HuR and miR‑29b‑3p and inhibits intestinal epithelial cell apoptosis in a mouse model of ulcerative colitis Yuxi Tian1 · Ying Wang2 · Fujun Li2 · Junwen Yang2 · Yan Xu3 · Miao Ouyang2 Received: 6 July 2020 / Accepted: 3 September 2020 © Japan Human Cell Society 2020
Abstract This study aimed to investigate the role of long non-coding RNA (lncRNA) taurine up-regulated 1 (TUG1) in the development of ulcerative colitis (UC) and to explore the underlying mechanisms. A murine model of UC was induced by dextran sodium sulfate (DSS) exposure. The colonic epithelial YAMC cells were treated with TNF-α to simulate the inflammatory environment of intestinal epithelial cells (IECs). RNA pull-down and RIP assays were performed to analyze the interaction between TUG1 and HuR. Luciferase activity assay was conducted to evaluate the interaction between TUG1 and miR29b-3p. Cell proliferation was evaluated by MTT assay. Cell apoptosis was assessed by flow cytometry and western blot analysis of apoptosis-related proteins. TUG1 overexpression promoted cell proliferation and inhibited cell apoptosis in the TNF-α-stimulated YAMC cells. The mechanistic analysis showed that TUG1 positively regulated the HuR/c-myc axis via its interaction with HuR, leading to upregulation of c-myc expression; meanwhile, TUG1 negatively regulated the miR29b-3p/CDK2 signaling via binding to miR-29b-3p, leading to derepression of CDK2 expression. Further animal experiments showed that TUG1 overexpression attenuated UC progression in the DSS-induced UC in mice. Collectively, TUG1 inhibits IEC apoptosis and UC progression by regulating the balance of HuR and miR-29b-3p. Keywords Ulcerative colitis · TUG1 · HuR · miR-29b-3p
Introduction
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s13577-020-00428-5) contains supplementary material, which is available to authorized users. * Yan Xu [email protected] * Miao Ouyang [email protected] 1
Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, China
2
Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, No. 87, Xiangya Road, Changsha, Hunan, China
3
Department of Health Care Center, Xiangya Hospital, Central South University, Changsha, No. 87, Xiangya Road, Changsha, Hunan, China
Ulcerative colitis (UC) is a chronic and uncontrolled inflammatory bowel disease (IBD) with an increasing incidence worldwide [1, 2]. UC is characterized by epithelial barrier damage and disruption of inflammatory homeostasis in the colon [3]. The disruption of the intestinal mucosal barrier homeostasis is the core event that causes the onset and progression of UC, and the abnormal apoptosis of intestinal epithelial cells (IECs) plays an important role in this event [4–6]. However, the etiology of UC has remained incompletely understood. Therefore, in-depth investigation of the mechanisms underlying UC may improve the clinical outcomes of UC. The epithelia
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