title: The loss of MiR-139-5p promotes colitis-associated tumorigenesis by mediating PI3K/AKT/Wnt signaling.
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.
authors.forename: Rurong
authors.initials: R
authors.lastname: Maoa
authors.forename: Fangyuan
authors.initials: F
authors.lastname: Zou
authors.forename: Liyan
authors.initials: L
authors.lastname: Yang
authors.forename: Shengchao
authors.initials: S
authors.lastname: Lin
authors.forename: Yueqi
authors.initials: Y
authors.lastname: Li
authors.forename: Mingxing
authors.initials: M
authors.lastname: Ma
authors.forename: Peihao
authors.initials: P
authors.lastname: Yin
authors.forename: Xin
authors.initials: X
authors.lastname: Liang
authors.forename: Jianwen
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000378:metabolism*; D003092:Colitis / Q000139:chemically induced / Q000473:pathology*; D003106:Colon / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000378:metabolism*; D016264:Dextran Sulfate; D018450:Disease Progression; D015870:Gene Expression; D045325:HCT116 Cells; D006801:Humans; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway
chemical_list: C546202:MIRN139 microRNA, mouse; D035683:MicroRNAs; D051153:Wnt Proteins; D016264:Dextran Sulfate; D019869:Phosphatidylinositol 3-Kinases; D017526:Receptor, IGF Type 1; D051057:Proto-Oncogene Proteins c-akt