To elucidate the mechanisms by which the mir-200 and the miR-183~96~182 cluster could regulate EMT and thus cellular migration, invasion and metastasis in NSCLC, we searched for common predicted targets of these microRNA families that might have a potential role in these biological processes. First we performed a cross comparison of multiple gene expression datasets from our mouse models of metastasis. We overlapped 224 genes that were elevated greater than four-folds upon Zeb1 induction in 393P cells with 210 genes that showed greater than two-fold increase in expression in the metastatic 344SQ cells compared to the non-metastatic 393P cells and 143 genes that were repressed to less than 0.5-fold in cells with exogenous expression of miR-200. This resulted in an enriched list of 45 genes that are potential miR-200 targets having a role in the process of EMT and metastasis. Next we performed an overlap of genes that were predicted targets of the miR-200 family members and the miR-183~96~182 cluster using the microRNA prediction algorithms miRanda (www.microRNA.org) and identified a list of 17 highly conserved common targets with a mirSVR score less than -6.0. The only 2 genes common in both the overlapping subsets were Zeb1 and Foxf2.
The miR-200 family and the miR-183~96~182 cluster target Foxf2 to inhibit invasion and metastasis in lung cancers.
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View SamplesMicroarray analysis of Myd88-/-Trif-/- and Myd88-/-Rip2-/- macrophage responses to WT or dotA mutant L. pneumophila.
Type IV secretion-dependent activation of host MAP kinases induces an increased proinflammatory cytokine response to Legionella pneumophila.
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