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Knockdown of lncRNA H19 inhibits abnormal differentiation of small intestinal epithelial cells in diabetic mice
Authors:Ti-Dong Shan  Shao-Yan Lv  Zi-Bin Tian  Xi-Shuang Liu  Fu-Guo Liu  Xu-Guo Sun
Institution:1. Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China;2. Department of Emergency Intensive Care Unit, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China

Ti-Dong Shan and Shao-Yan Lv contributed equally to this work.

Abstract:Diabetes mellitus (DM) comprises a group of metabolic diseases characterized by insulin deficiency or resistance and hyperglycemia. We previously reported the presence of abnormal differentiation of small intestinal epithelial cells (IECs) in diabetic mice, but the exact mechanism of this phenomenon has not been thoroughly elucidated to date. In this study, we found that H19 was markedly upregulated in IECs of DM mice. H19 knockdown significantly inhibited abnormal differentiation of IECs in DM mice. Bioinformatics analysis identified miR-141-3p as a candidate for H19. Based on luciferase reporter assays, we found that miR-141-3p directly targeted H19. Luciferase reporter assays also showed that miR-141-3p could directly target β-catenin. Furthermore, H19 might act as an endogenous “sponge” by competing for miR-141-3p binding to regulate miRNA targets in vitro and in vivo. In summary, our findings provide the first evidence supporting the role of H19 in IECs of DM mice, and miR-141-3p targets not only protein-coding genes but also the lncRNA H19.
Keywords:diabetes mellitus  differentiation  intestinal epithelial cell  lncRNA  microRNA
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