Wnt信号通路
癌变
结肠炎
癌症研究
PI3K/AKT/mTOR通路
生物
蛋白激酶B
基因剔除小鼠
结直肠癌
转基因小鼠
转基因
连环素
信号转导
癌症
免疫学
细胞生物学
基因
遗传学
作者
Rurong Mao,Fangyuan Zou,Liyan Yang,Shengchao Lin,Yueqi Li,Mingxing Ma,Peihao Yin,Xin Liang,Jianwen Liu
标识
DOI:10.1016/j.biocel.2015.10.008
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 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.
科研通智能强力驱动
Strongly Powered by AbleSci AI