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

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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Author(s)

  • Linjie Zhao
  • Wei Wang
  • Lian Xu
  • Tao Yi
  • Xia Zhao
  • Yuquan Wei
  • Louis Vermeulen
  • Ajay Goel
  • Shengtao Zhou

Detail(s)

Original languageEnglish
Pages (from-to)2305-2319
Journal / PublicationOncogene
Volume38
Issue number13
Online published26 Nov 2018
Publication statusPublished - 28 Mar 2019

Link(s)

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 down-regulation, 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.

Research Area(s)

Citation Format(s)

Integrative network biology analysis identifies miR-508-3p as the determinant for the mesenchymal identity and a strong prognostic biomarker of ovarian cancer. / Zhao, Linjie; Wang, Wei; Xu, Lian; Yi, Tao; Zhao, Xia; Wei, Yuquan; Vermeulen, Louis; Goel, Ajay; Zhou, Shengtao; Wang, Xin.

In: Oncogene, Vol. 38, No. 13, 28.03.2019, p. 2305-2319.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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