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 0 -untranslated region (3 0 -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.
BackgroundInflammatory response markers have been proposed to predict the clinical outcomes in various cancers. The aim of this study was to explore the influence of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) on the prognosis of osteosarcoma.MethodsThree hundred fifty-nine patients who underwent curative surgery for osteosarcoma were enrolled from 2005 to 2010. NLR and PLR were calculated from peripheral blood cell counts taken at pre-treatment. Optimal cutoff values of NLR and PLR were determined on the basis of receiver operating characteristic curve analysis. A predictive model was established to predict the clinical outcome for overall survival, and the predictive accuracy of this model was determined by concordance index (c-index).ResultsOur results showed that advanced stage and metastasis at diagnosis were significantly associated with the high NLR and PLR groups. NLR was an independent prognostic indicator for overall survival (HR = 1.80, 95 % CI = 1.35–2.41, P < 0.001) and progression-free survival (HR = 1.65, 95 % CI = 1.26–2.15, P < 0.001), except for PLR. The nomogram could perform well in the prediction of overall survival in patients with osteosarcoma (c-index 0.829).ConclusionsOur results suggest that both NLR and PLR can reflect clinical prognosis. NLR is more predictive of overall survival and progression-free survival than PLR.
Abstract. microRNAs are involved in different cancer-related processes. miR-195, one of the miR-16/15/195/424/497 family members, has been shown to act as a tumor suppressor during tumorigenesis. However, the function of miR-195 in osteosarcoma is still unclear. In our study, the miR-195 expression level was upregulated in osteosarcoma cells, by transfection with miR-195, and the fatty acid synthase (FASN) mRNA and protein expression levels were measured by RT-PCR and western blotting. Cell migration and invasion was measured using wound healing migration and Transwell invasion assays. We found that the upregulation of miR-195 greatly decreased cell invasion and the migration of U2OS. We also identified that FASN may be a direct target of miR-195 by the luciferase activity assay. These findings provide evidence that miR-195 plays a key role in inhibiting osteosarcoma cell migration and invasion through targeting FASN, and strongly suggest that exogenous miR-195 may have therapeutic value in treating osteosarcoma.
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