MiR-196a Is Upregulated in Gastric Cancer and Promotes Cell Proliferation by Downregulating p27 kip1

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 p27kip1 expression by targeting one binding site in the 3′-untranslated region (3′-UTR) of p27kip1 mRNA. qPCR and Western blot assays verified that miR-196a reduced p27kip1 expression at both mRNA and protein levels. The p27kip1-mediated repression in cell proliferation was reverted by exogenous miR-196a expression. A reverse correlation between miR-196a and p27kip1 expression was noted in gastric cancer tissues. Our study shows that aberrant overexpression of miR-196a and consequent downregulation of p27kip1 could contribute to gastric carcinogenesis and would be targets for gastric cancer therapies and further developed as potential prognostic factors. Mol Cancer Ther; 11(4); 842–52. ©2012 AACR .