Integrative network biology analysis identifies miR-508-3p as the determinant for the mesenchymal identity and a strong prognostic biomarker of ovarian cancer.

Authors

Oncogene 2018, doi:https://doi.org/10.1038/s41388-018-0577-5

Abstract

Ovarian cancer is a heterogeneous malignancy that poses tremendous clinical challenge. Based on unsupervised classification of whole-genome gene expression profiles, four molecular subtypes of ovarian cancer were recently identified. However, single-driver molecular events specific to these subtypes have not been clearly elucidated.

We aim to characterize the regulatory mechanisms underlying the poor prognosis mesenchymal subtype of ovarian cancer using a systems biology approach, involving a variety of molecular modalities including gene and microRNA expression profiles. miR-508-3p emerged as the most powerful determinant that regulates a cascade of dysregulated genes in the mesenchymal subtype, including core genes involved in epithelial–mesenchymal transition (EMT) program.

Moreover, miR-508-3p downregulation, due to promoter hypermethylation, was directly correlated with metastatic behaviors in vitro and in vivo. Taken together, our multidimensional network analysis identified miR-508-3p as a master regulator that defines the mesenchymal subtype and provides a novel prognostic biomarker to improve management of this disease.

Keywords

Ovarian Cancer, Network, miR-508-3p, Biomarker, Mesenchymal

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