title: Tumor-suppressive microRNA-195-5p regulates cell growth and inhibits cell cycle by targeting cyclin dependent kinase 8 in colon cancer.
abstract: MicroRNAs (miRNAs) are key regulators in gene expression. Dysregulation of them in cancer development have been attracting increasing attention. The purpose of this study was to investigate the potential role of miR-195-5p in colon cancer (CC) biology. Expression of miR-195-5p in CC specimens and adjacent normal tissues were measured by quantitative polymerase chain reaction (qPCR). Overexpression of miR-195-5p was established by transfecting mimics into SW480 CC cells. Following, MTT assays, wound healing assays, invasion assays and cell cycle assays were used to explore the potential function of miR-195-5p in SW480 cells. Dual-luciferase reporter assays were performed to validate the regulation of a putative target of miR-195-5p, in corroboration with qPCR and western blot assays. The expression of miR-195-5p in CC specimens was significantly lower than that of adjacent normal tissues (P < 0.05). Overexpression of miR-195-5p inhibited cellular growth, suppressed cellular migration and invasion, and led to cell cycle arrest at G1 phase in vitro. Dual-luciferase reporter assays showed that miR-195-5p binds the 3'-untranslated region (UTR) of CDK8, suggesting that CDK8 should be a direct target of miR-195-5p. Moreover, qPCR and western blot assays confirmed CDK8 mRNA and protein levels were reduced after overexpression of miR-195-5p. These findings are supportive of miR-195-5p as a novel tumor suppressor in CC, thus may serve as a new strategy for cancer treatment.
authors.affiliation: Department of Gastrointestinal Surgery, Shanghai East Hospital, Tongji University School of Medicine Shanghai 200120, P. R. China.
authors.forename: Qifeng
authors.initials: Q
authors.lastname: Luo
authors.affiliation: Department of Gastrointestinal Surgery, Shanghai East Hospital, Tongji University School of Medicine Shanghai 200120, P. R. China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Gastrointestinal Surgery, Shanghai East Hospital, Tongji University School of Medicine Shanghai 200120, P. R. China.
authors.forename: Zhenling
authors.initials: Z
authors.lastname: Dai
authors.affiliation: Department of Gastrointestinal Surgery, Shanghai East Hospital, Tongji University School of Medicine Shanghai 200120, P. R. China.
authors.forename: Shiva
authors.initials: S
authors.lastname: Basnet
authors.affiliation: Department of Research Administration, Shanghai East Hospital, Tongji University School of Medicine Shanghai 200120, P. R. China.
authors.forename: Shuping
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine Shanghai 200072, P. R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
authors.affiliation: Department of Gastrointestinal Surgery, Shanghai East Hospital, Tongji University School of Medicine Shanghai 200120, P. R. China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Ge
keywords: CDK8; MiR-195-5p; SW480; cell cycle; colon cancer