MiRNA-mediated induction of mesenchymal-to-epithelial transition (MET) between cancer cell types is significantly modulated by inter-cellular molecular variability

ABSTRACT: Recent years have witnessed a dramatic increase in our appreciation of the contribution of microRNAs (miRNAs) to cancer onset and progression. As a consequence, there has been growing interest in the development of miRNAs not only as diagnostic biomarkers of cancer but also as a promising new class of therapeutic agents. Over the last several years, our laboratory has focused on analysis of the molecular processes underlying the ability of individual miRNAs to induce mesenchymal-to-epithelial transition (MET) particularly in ovarian cancer. Ectopic over expression of specific miRNAs down regulated during epithelial-to mesenchymal transition (EMT) have previously been reported to induce MET in a variety of cancer cells, thereby reducing metastatic potential and resistance to standard-of-care chemotherapies. Interestingly, the ability of individual miRNAs to induce MET when over expressed in cancer cells is often cancer/cell-type specific. In an effort to better understand the molecular processes underlying this specificity, we examined the molecular and phenotypic responses of three mesenchymal-like cancer cell lines (two ovarian and one prostate) to ectopic over expression of three sequentially divergent miRNAs previously implicated in the EMT/MET process. The ability of these sequentially divergent miRNAs to induce MET in these cells was found to be associated with inherent differences in the starting molecular profiles of the untreated cancer cells and specifically, variability in trans-regulatory controls modulating the expression of genes targeted by the individual miRNAs. While our results support the view that miRNAs have significant potential as cancer therapeutic agents, our findings further indicate that optimal treatments will likely need to be personalized with respect to the molecular profiles of the individual cancers being treated.

ORGANISM(S): Homo sapiens

PROVIDER: GSE130402 | GEO | 2020/04/03

REPOSITORIES: GEO