Overexpression of miR-429 induces mesenchymal-to-epithelial transition (MET) in metastatic ovarian cancer cells

ObjectiveOvarian cancer (OC) is the most lethal of all gynecological malignancies primarily due to the sloughing-off of highly metastatic cells from primary tumors and their subsequent spread throughout the peritoneal cavity. Since the epithelial-to-mesenchymal transition (EMT) of OC cells located at the periphery of primary tumors is essential to this process, molecular interventions that can block EMT are of potential clinical significance. Members of the miR200 family of microRNAs have been implicated in EMT in other cancers. Our purpose was to determine if miR200 family microRNAs may be involved in EMT in OC and of potential therapeutic value in reducing OC metastasis.MethodsGene expression profiles of two OC cell lines with different metastatic potentials were monitored using qRT-PCR (quantitative reverse transcription polymerase chain reaction). The effect of over-expression of a miR-200 family microRNA (miR-429) in metastatic OC cells was monitored on molecular (qRT-PCR and microarray) and functional (morphology, migration, invasiveness and anchorage independence assays) levels.ResultsMolecular profiling of two OC cell lines with differing metastatic potentials identified significant differences in previously established epithelial and mesenchymal cell biomarkers including E-cadherin, ZEB1, ZEB2, miR-205 and miR-200 family microRNAs. Ectopic overexpression of miR-429, a member of the miR-200 family of microRNAs, in mesenchymal-like OC cells resulted in reversal of the mesenchymal phenotype (mesenchymal-epithelial transition, MET).ConclusionsOur results indicate that miR-429 may not only be a useful biomarker of EMT in ovarian cancer, but also of potential therapeutic value in abating OC metastasis.

Research Highlights► miR-429 induces MET in a highly metastatic ovarian cancer cell line. ► Most miR-429 induced molecular changes are indirect. ► miR-429 may be of therapeutic value in reducing OC metastasis and tumor recurrence.