期刊
FEBS JOURNAL
卷 283, 期 8, 页码 1438-1452出版社
WILEY
DOI: 10.1111/febs.13678
关键词
acute colitis; apoptosis; colitis-associated colorectal cancer; miR-139-5p; proliferation
资金
- Shanghai Committee of Science and Technology [13140902300, 13401900502, 11DZ2260600]
- National Natural Science Foundation of China [81502540]
- Fundamental Research Fund for the Central Universities of China [222201514333]
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.
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