title: MicroRNA profiling in Muc2 knockout mice of colitis-associated cancer model reveals epigenetic alterations during chronic colitis malignant transformation.
abstract: Our previous studies have demonstrated that genetic deletion of the Muc2 gene causes colorectal cancers in mice. The current study further showed that at the early stage (<3 months) the Muc2 knockout mice spontaneously developed chronic inflammation in colon and rectum, similar pathological features as human colitis; and at the late stage (>3 months) the mice exhibited colorectal cancer, including a unique phenotype of rectal prolapsed (rectal severe inflammation and adenocarcinoma). Thus, the age of 3 months might be the key point of the transition from chronic inflammation to cancer. To determine the mechanisms of the malignant transformation, we conducted miRNA array on the colonic epithelial cells from the 3-month Muc2-/- and +/+ mice. MicroRNA profiling showed differential expression of miRNAs (i.e. lower or higher expression enrichments) in Muc2-/- mice. 15 of them were validated by quantitative PCR. Based on relevance to cytokine and cancer, 4 miRNAs (miR-138, miR-145, miR-146a, and miR-150) were validate and were found significantly downregulated in human colitis and colorectal cancer tissues. The network of the targets of these miRNAs was characterized, and interestedly, miRNA-associated cytokines were significantly increased in Muc2-/-mice. This is the first to reveal the importance of aberrant expression of miRNAs in dynamically transformation from chronic colitis to colitis-associated cancer. These findings shed light on revealing the mechanisms of chronic colitis malignant transformation.
authors.affiliation: Department of Immunology, Xinxiang Medical University, Xinxiang, China.
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Bao
authors.affiliation: Department of Laboratory Medicine, Xinxiang Medical University, Xinxiang, China.
authors.forename: Yongchen
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Surgery, the First Affiliated Hospital of Xinxiang Medical University, Weihui, China.
authors.forename: Zexin
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China.
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Fang
authors.affiliation: School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China.
authors.forename: Yiqiong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China.
authors.forename: Xuhan
authors.initials: X
authors.lastname: Li
authors.affiliation: School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China.
authors.forename: Zhuangzhuang
authors.initials: Z
authors.lastname: Li
authors.affiliation: School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China.
authors.forename: Bowen
authors.initials: B
authors.lastname: Xiong
authors.affiliation: School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Surgery, the First Affiliated Hospital of Xinxiang Medical University, Weihui, China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Wang
authors.affiliation: School of Life Sciences, Shenzhen University, Shenzhen, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Kang
authors.affiliation: School of Life Sciences, Shenzhen University, Shenzhen, China.
authors.forename: Deming
authors.initials: D
authors.lastname: Gou
authors.affiliation: School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China; Department of Pathology, University of Illinois at Chicago, Chicago, Illinois, United States of America.
authors.forename: Wancai
authors.initials: W
authors.lastname: Yang
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000378:metabolism; D002908:Chronic Disease; D003092:Colitis / Q000378:metabolism* / Q000473:pathology; D003106:Colon / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000378:metabolism*; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D055262:Mucin-2 / Q000235:genetics*; D012007:Rectum / Q000378:metabolism / Q000473:pathology; D059467:Transcriptome
chemical_list: D035683:MicroRNAs; C524626:Muc2 protein, mouse; D055262:Mucin-2