MiR-196a Is Up-regulated In Gastric Cancer And Promotes Cell Proliferation By Down-regulating P27^kip1

Gastric carcinogenesis is a multi-steps process that involves the proto-oncogenes andtumor suppressor genes, genetic and epigenetic changes. Recent studies showed thatmiRNA could play a similar role in oncogenes or tumor suppressor genes byregulating target genes to participate in related signaling pathways, and impact tumorinvasion and metastasis process, Aberrant expression of miR-196a has beenfrequently reported in cancer studies. However, the expression and mechanism of itsfunction in gastric cancer（GC） remains unclear. Real-time quantitative PCR wasperformed to detect the relative expression of miR-196a in GC cell lines and tissues.SGC7901cells were treated with miR-196a inhibitors, mimics, orpCDNA/miR-196a to investigate the role of miR-196a in cell proliferation. Higherexpression of miR-196a in GC tissues was associated with tumor size, a higherclinical stage, and was also correlated with shorter overall survival of GC patients.Exogenous downregulation of miR-196a expression significantly suppressed the invitro cell cycle progression, proliferation and colony formation of GC cells, and ectopic miR-196a expression significantly enhanced the development of tumors innude mice. Luciferase assays revealed that miR-196a inhibited p27^kip1expression bytargeting one binding site in the3′-untranslated region （3′UTR） of p27^kip1mRNA.QPCR and western blot assays verified that miR-196a reduced p27^kip1expression atboth mRNA and protein levels. The p27^kip1-mediated repression in cell proliferationwas reverted by exogenous miR-196a expression. A reverse correlation betweenmiR-196a and p27^kip1expression was noted in GC tissues. Our study demonstratesthat aberrant over-expression of miR-196a and consequent down-regulation ofp27^kip1could contribute to gastric carcinogenesis, and would be targets for gastriccancer therapies and further developed as potential prognostic factors.