title: Coactivator-associated arginine methyltransferase 1 promotes cell growth and is targeted by microRNA-195-5p in human colorectal cancer.
abstract: The pathogenesis of colorectal cancer remains poorly understood. Here, we show that coactivator-associated arginine methyltransferase 1 is frequently upregulated in colorectal cancer tissues and promotes cell growth in vitro and in vivo. Using bioinformatics-based prediction and luciferase reporter system, we found that coactivator-associated arginine methyltransferase 1 is post-transcriptionally targeted by microRNA-195-5p in colorectal cancer. Ectopic expression of microRNA-195-5p led to the suppression of the coactivator-associated arginine methyltransferase 1 3'-untranslated regions activity and downregulation of the endogenous coactivator-associated arginine methyltransferase 1 protein in colorectal cancer cells. Expression analysis verified that microRNA-195-5p was markedly downregulated in human colorectal cancer tissues, which was negatively correlated with the elevated levels of coactivator-associated arginine methyltransferase 1 protein. Enhanced levels of microRNA-195-5p in colorectal cancer cells resulted in a sharp reduction of cell proliferative and colony-formative capacities in vitro. Remarkably, restoration of coactivator-associated arginine methyltransferase 1 in microRNA-195-5p-transfected colorectal cancer cells partially abrogated the inhibition of cell proliferation and colony formation mediated through microRNA-195-5p. These data confirm that microRNA-195-5p might function as an anti-tumor microRNA in colorectal cancer exerting critical control over coactivator-associated arginine methyltransferase 1 expression. The newly identified microRNA-195-5p/coactivator-associated arginine methyltransferase 1 axis may act as a novel promising therapeutic target for colorectal cancer treatment.
authors.affiliation: Department of General Surgery, Xinhua Hospital, Chongming Branch, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
authors.forename: Meifeng
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Xinhua Hospital, Chongming Branch, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of General Surgery, Xinhua Hospital, Chongming Branch, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: Gao
authors.affiliation: Department of General Surgery, Xinhua Hospital, Chongming Branch, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Xinhua Hospital, Chongming Branch, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
authors.forename: Xinde
authors.initials: X
authors.lastname: Ding
authors.affiliation: Department of General Surgery, Xinhua Hospital, Chongming Branch, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
authors.forename: Ronghua
authors.initials: R
authors.lastname: Zhu
authors.affiliation: Department of General Surgery, Xinhua Hospital, Chongming Branch, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
authors.forename: Haiqun
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of General Surgery, Xinhua Hospital, Chongming Branch, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
authors.forename: Zhewei
authors.initials: Z
authors.lastname: Fei
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000368:Aged; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D011484:Protein-Arginine N-Methyltransferases / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D015854:Up-Regulation
chemical_list: D020413:3' Untranslated Regions; C552722:MIRN195 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; D011484:Protein-Arginine N-Methyltransferases; C119966:coactivator-associated arginine methyltransferase 1
keywords: Colorectal cancer; coactivator-associated arginine methyltransferase 1; colony formation; microRNA-195-5p; proliferation