文献类型：期刊文献

英文题名：Targeted deletion of miR-139-5p activates MAPK, NF-B and STAT3 signaling and promotes intestinal inflammation and colorectal cancer

作者：Zou, Fangyuan[1,2];Mao, Rurong[1,2];Yang, Liyan[1,2];Lin, Shengchao[1,2];Lei, Kecheng[1,2];Zheng, Yuanhong[1,2];Ding, Yue[1,2];Zhang, Peng[1,2];Cai, Guoxiang[3,4];Liang, Xin[1,2];Liu, Jianwen[1,2]

机构：[1]E China Univ Sci & Technol, Sch Pharm, State Key Lab Bioreactor Engn, 268,130 Meilong Rd, Shanghai 200237, Peoples R China;[2]E China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, 268,130 Meilong Rd, Shanghai 200237, Peoples R China;[3]Fudan Univ, Shanghai Canc Ctr, Dept Colorectal Surg, Shanghai 200032, Peoples R China;[4]Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai, Peoples R China

年份：2016

卷号：283

期号：8

起止页码：1438

外文期刊名：FEBS JOURNAL

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000374680500006)】；

基金：This work was supported by the Shanghai Committee of Science and Technology (No. 13140902300 and 13401900502), a Shanghai Committee of Science and Technology grant (11DZ2260600) and National Natural Science Foundation of China (No. 81502540), Fundamental Research Fund for the Central Universities of China (No. 222201514333). The authors declare that they have no conflicts of interest.

语种：英文

外文关键词：acute colitis; apoptosis; colitis-associated colorectal cancer; miR-139-5p; proliferation

摘要：miR-139-5p, which has been reported to be underexpressed in several types of cancer, is associated with tumorigenesis by participating in various biological processes via the modulation of different target genes. In the present study, we analyzed mice deficient in miR-139-5p, aiming to investigate its role in intestinal inflammation and colitis-associated colorectal cancer. We show that miR-139-5p knockout (KO) mice are highly susceptible to colitis and colon cancer, accompanied by elevated proliferation and decreased apoptosis, as well as an increased production of inflammatory cytokines, chemokines and tumorigenic factors. Furthermore, enhanced colon inflammation and colorectal tumor development in miR-139-5p KO mice are a result of the regulatory effects of miR-139-5p on its target genes for Rap1b and nuclear factor-kappa B, thus affecting the activity of the mitogen-activated protein kinase, nuclear factor-kappa B and signal transducer and activator of transcription 3 signaling pathways. These results reveal a critical part for miR-139-5p in maintaining intestinal homeostasis and protecting against colitis and colorectal cancer in vivo, providing new insights into the function of miR-139-5p with respect to linking inflammation to carcinogenesis.