MiR-182 and miR-203 induce mesenchymal to epithelial transition and self-sufficiency of growth signals via repressing SNAI2 in prostate cells

Abstract

MicroRNAs play critical roles in tumorigenesis and metastasis. Here, we report the dual functions of miR-182 and miR-203 in our previously described prostate cell model. MiR-182 and miR-203 were completely repressed during epithelial to mesenchymal transition (EMT) from prostate epithelial EP156T cells to the progeny mesenchymal nontransformed EPT1 cells. Re-expression of miR-182 or miR-203 in EPT1 cells and prostate cancer PC3 cells induced mesenchymal to epithelial transition (MET) features. Simultaneously, miR-182 and miR-203 provided EPT1 cells with the ability to self-sufficiency of growth signals, a well-recognized oncogenic feature. Gene expression profiling showed high overlap of the genes affected by miR-182 and miR-203. SNAI2 was identified as a common target of miR-182 and miR-203. Knock-down of SNAI2 in EPT1 cells phenocopied re-expression of either miR-182 or miR-203 regarding both MET and self-sufficiency of growth signals. Strikingly, considerable overlaps of changed genes were found between the re-expression of miR-182/203 and knock-down of SNAI2. Finally, P-cadherin was identified as a direct target of SNAI2. We conclude that miR-182 and miR-203 induce MET features and growth factor independent growth via repressing SNAI2 in prostate cells. Our findings shed new light on the roles of miR-182/203 in cancer related processes. What's new? While alterations in micro-RNA (miRNA) expression have been implicated in the pathogenesis of human malignancies, they have not been investigated extensively in pre-malignant cells. Here, re-expression of the miRNAs miR-182 and miR-203 in mesenchymal non-transformed prostate cancer (EPT1) cells was found to induce mesenchymal to epithelial transition (MET) features and self-sufficiency of growth signals. The acquisition of the oncogenic characteristics was mediated through repression of SNAI2, which was demonstrated to be a common target of miR-182 and miR-203. The dual functions of these molecules shed light on their complex mechanisms in tumor progression. Copyright © 2013 UICC.