title: MiR-196a is upregulated in gastric cancer and promotes cell proliferation by downregulating p27(kip1).
abstract: Aberrant expression of miR-196a has been frequently reported in cancer studies. However, the expression and mechanism of its function in gastric cancer remains unclear. Quantitative real-time PCR was carried out to detect the relative expression of miR-196a in gastric cancer cell lines and tissues. SGC7901 cells were treated with miR-196a inhibitors, mimics, or pCDNA/miR-196a to investigate the role of miR-196a in cell proliferation. Higher expression of miR-196a in gastric cancer tissues was associated with tumor size, a higher clinical stage, and was also correlated with shorter overall survival of patients with gastric cancer. Exogenous downregulation of miR-196a expression significantly suppressed the in vitro cell-cycle progression, proliferation, and colony formation of gastric cancer cells, and ectopic miR-196a expression significantly enhanced the development of tumors in nude mice. Luciferase assays revealed that miR-196a inhibited p27(kip1) expression by targeting one binding site in the 3'-untranslated region (3'-UTR) of p27(kip1) mRNA. qPCR and Western blot assays verified that miR-196a reduced p27(kip1) expression at both mRNA and protein levels. The p27(kip1)-mediated repression in cell proliferation was reverted by exogenous miR-196a expression. A reverse correlation between miR-196a and p27(kip1) expression was noted in gastric cancer tissues. Our study shows that aberrant overexpression of miR-196a and consequent downregulation of p27(kip1) could contribute to gastric carcinogenesis and would be targets for gastric cancer therapies and further developed as potential prognostic factors.
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, PR China.
authors.forename: Ming
authors.initials: M
authors.lastname: Sun
authors.forename: Xiang-hua
authors.initials: XH
authors.lastname: Liu
authors.forename: Jin-hai
authors.initials: JH
authors.lastname: Li
authors.forename: Jin-song
authors.initials: JS
authors.lastname: Yang
authors.forename: Er-bao
authors.initials: EB
authors.lastname: Zhang
authors.forename: Dan-dan
authors.initials: DD
authors.lastname: Yin
authors.forename: Zhi-li
authors.initials: ZL
authors.lastname: Liu
authors.forename: Jing
authors.initials: J
authors.lastname: Zhou
authors.forename: Ying
authors.initials: Y
authors.lastname: Ding
authors.forename: Su-qin
authors.initials: SQ
authors.lastname: Li
authors.forename: Zhao-xia
authors.initials: ZX
authors.lastname: Wang
authors.forename: Xiu-feng
authors.initials: XF
authors.lastname: Cao
authors.forename: Wei
authors.initials: W
authors.lastname: De
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014162:Transfection; D015854:Up-Regulation
chemical_list: C436291:CDKN1B protein, human; C542543:MIRN196 microRNA, human; D035683:MicroRNAs; D050760:Cyclin-Dependent Kinase Inhibitor p27