The loss of MiR-139-5p promotes colitis-associated tumorigenesis by mediating PI3K/AKT/Wnt signaling. (December 2015)

• Record Type: Journal Article
• Authors: Mao, Rurong; Zou, Fangyuan; Yang, Liyan; Lin, Shengchao; Li, Yueqi; Ma, Mingxing; Yin, Peihao; Liang, Xin; Liu, Jianwen
• Is Part Of: International journal of biochemistry & cell biology. Volume 69(2015:Dec.)
• Page Start: 153
• Page End: 161
• Publication Date: 2015-12
• Subjects: CAC colitis-associated cancer -- CRC colorectal carcinoma -- MicroRNAs miRNAs -- IGF-1R type I insulin-like growth factor receptor -- AOM azoxymethane -- DSS dextran sodium sulfate -- P13K phosphatidylinositol 3 kinase -- IHC immunohistochemistry -- siRNA small interfering RNA -- KO knockout; Transgenic murine model -- CAC -- MiR-139-5p -- β-Catenin -- IGF-1R; Biochemistry -- Periodicals; Cytology -- Periodicals; Biochemistry -- Periodicals; Cell Biology -- Periodicals; Biochimie -- Périodiques; Cytologie -- Périodiques; Biochimie; Cytologie; Biochemistry; Cytology; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); Periodicals; 572.05
• DOI: 10.1016/j.biocel.2015.10.008
• Languages: English
• ISSNs: 1357-2725

Abstract

Graphical abstract: Abstract: 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 β-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.