miR-186 Downregulation Correlates with Poor Survival in Lung Adenocarcinoma, Where It Interferes with Cell-Cycle Regulation

摘要: Deeper mechanistic understanding of lung adenocarcinoma (non–small cell carcinoma, or NSCLC), a leading cause cancer-related deaths overall, may lead to more effective therapeutic strategies. In analyzing NSCLC clinical specimens and lines, we discovered uniform decrease in miR-186 ( MIR186 ) expression comparison with normal tissue epithelial lines. correlated patient survival, median overall survival time 63.0 21.5 months cases exhibiting high low levels miR-186, respectively. Enforced overexpression cells inhibited proliferation by inducing G 1 –S checkpoint arrest. Conversely, RNA interference–mediated silencing promoted cell-cycle progression accelerated the cells. Cyclin D1 CCND1 ), cyclin-dependent kinase (CDK)2, CDK6 were each directly targeted for inhibition restoring their reversed miR-186–mediated progression. The inverse relationship between its targets was confirmed tumor xenografts specimens. Taken together, our findings established tumor-suppressive role NSCLC. Cancer Res; 73(2); 756–66. ©2012 AACR .