Analysis of metastatic-repressing microRNAs and determining ZEB1 as a gene candidate for siRNA knockout in mesenchymal-like ovarian and prostate cancer cell lines

Abstract

MicroRNAs (miRNAs) have been shown to play a significant role in cancer progression and metastasis through their regulation of gene expression to activate epithelial-mesenchymal transition (EMT). Understanding the genetic and molecular basis for how microRNAs induce EMT’s reciprocal mechanism, mesenchymal-epithelial transition (MET), is vital as metastatic disease is highly lethal. This study aims to identify genes involved in MET across two cancer types based on microRNA overexpressions that have previously been shown to induce MET in mesenchymal-like ovarian or prostate cancer cell lines. It also aims to understand how the same microRNAs behave in similar mesenchymal cell-lines. To elucidate the ability of different microRNAs to induce the same process of MET in two reproductive cancer cell lines, transfections to overexpress miR-429, miR-203a, and miR-205 in both ovarian cancer and prostate cancer cell lines, HEY and PC3, respectively, were performed. Using microarray analysis, differentially expressed genes were identified and comparisons of these genes to known EMT/MET genes was done to narrow down a set of genes important in both ovarian and prostate cancer MET processes. We show that miR-429 induces MET in both HEY and PC3 cells, but not through similar pathways, and that overexpression of miR-203a and miR-205 induced MET in either HEY or PC3, but not both. ZEB1 was identified as a gene candidate for siRNA knockout to recapitulate MET and further elucidate mechanisms of the three microRNAs inducing MET.