title: Targeted deletion of miR-139-5p activates MAPK, NF-κB and STAT3 signaling and promotes intestinal inflammation and colorectal cancer.
abstract: 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.
authors: State Key Laboratory of Bioreactor Engineering & Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, China.
authors: Fangyuan
authors: F
authors: Zou
authors: State Key Laboratory of Bioreactor Engineering & Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, China.
authors: Rurong
authors: R
authors: Mao
authors: State Key Laboratory of Bioreactor Engineering & Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, China.
authors: Liyan
authors: L
authors: Yang
authors: State Key Laboratory of Bioreactor Engineering & Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, China.
authors: Shengchao
authors: S
authors: Lin
authors: State Key Laboratory of Bioreactor Engineering & Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, China.
authors: Kecheng
authors: K
authors: Lei
authors: State Key Laboratory of Bioreactor Engineering & Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, China.
authors: Yuanhong
authors: Y
authors: Zheng
authors: State Key Laboratory of Bioreactor Engineering & Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, China.
authors: Yue
authors: Y
authors: Ding
authors: State Key Laboratory of Bioreactor Engineering & Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, China.
authors: Peng
authors: P
authors: Zhang
authors: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, China.|Department of Oncology, Shanghai Medical College, Fudan University, China.
authors: Guoxiang
authors: G
authors: Cai
authors: State Key Laboratory of Bioreactor Engineering & Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, China.
authors: Xin
authors: X
authors: Liang
authors: State Key Laboratory of Bioreactor Engineering & Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, China.
authors: Jianwen
authors: J
authors: Liu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D003092:Colitis / Q000139:chemically induced / Q000150:complications / Q000473:pathology; D015179:Colorectal Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D007124:Immunoenzyme Techniques; D007249:Inflammation / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C546202:MIRN139 microRNA, mouse; D035683:MicroRNAs; D016328:NF-kappa B; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; D020928:Mitogen-Activated Protein Kinases
keywords: acute colitis; apoptosis; colitis-associated colorectal cancer; miR-139-5p; proliferation