An integrative network biology analysis identifies miR-508-3p as the determinant and a prognosis biomarker of the mesenchymal subtype ovarian cancer

Recently, several research groups have identified the mesenchymal subtype of serous OvCa on the basis of transcriptome data and its potential correlation with poor prognosis. We set out to define the regulatory mechanisms underlying the distinct gene expression profiles of serous OvCa using a network-based approach involving multiple molecular modalities such as gene expression and microRNA (miR) expression. Our study demonstrated that the mir-508-3p presented as the most powerful determinant of mesenchymal subtype-specific gene expression, tuning the majority of genes differentially expressed in the poor prognosis subtype, including genes associated with the epithelial–mesenchymal transition (EMT) program. Consequent functional experiments illustrate that miR-508-3p inhibition promoted EMT process, in vitro cell migration and invasion, and in vivo cancer metastasis. Overall design: Total RNA was isolated after treatment with control miRNA or miR-508-3p inhibitor in OVTOKO and OVISE cell lines. Two independent experiments were carried out and gene expression profiles were analyzed.