文献类型：期刊文献

英文题名：The loss of MiR-139-5p promotes colitis-associated tumorigenesis by mediating PI3K/AKT/Wnt signaling

作者：Mao, Rurong[1,2];Zou, Fangyuan[1,2];Yang, Liyan[1,2];Lin, Shengchao[1,2];Li, Yueqi[1,2];Ma, Mingxing[1,2];Yin, Peihao[3];Liang, Xin[1,2];Liu, Jianwen[1,2]

机构：[1]E China Univ Sci & Technol, Sch Pharm, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]E China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China;[3]Shanghai Univ Tradit Chinese Med, Putuo Hosp, Dept Gen Surg, Shanghai 200062, Peoples R China

年份：2015

卷号：69

起止页码：153

外文期刊名：INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000367020800017)】；

基金：This work was supported by Shanghai Committee of Science and Technology (Nos. 13140902300, 13401900502 and grant 11DZ2260600).

语种：英文

外文关键词：Transgenic murine model; CAC; MiR-139-5p; beta-Catenin; IGF-1R

摘要：MiR-139-5p down-regulation has frequently been implicated in colorectal carcinoma. However, there is little known about its biological function between inflammation and cancer in vivo. Here, a transgenic murine model of colorectal carcinoma was used to investigate pathogenetic role of miR-139-5p in colitis and colitis-associated tumorigenesis. We showed that miR-139-5p knockout mice were higher sensitive to DSS-induced colitis and enhanced formation of intestinal neoplasia was observed when mice were exposed to AOM/DSS treatment. MiR-139-5p knockout mice exhibited an increased expression of genes involved in Wnt pathway. Such genes are closely associated with cell proliferation and differentiation, promoting the beta-catenin nuclear accumulation. Furthermore, biochemical studies in HCT-116 cells revealed that the over-expression of miR-139-5p inhibited the crosstalk between PI3K/AKT and Wnt pathway mediated by IGF-1R. Collectively, these findings indicate that miR-139-5p plays a crucial role in the development and progression of colitis-associated tumorigenesis and suggest that miR-139-5p may serve as a potential therapeutic target for the treatment of colitis-associated cancer in the future. (C) 2015 Elsevier Ltd. All rights reserved.