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 journal › peer-review
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Original language | English |
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Pages (from-to) | 2305-2319 |
Journal / Publication | Oncogene |
Volume | 38 |
Issue number | 13 |
Online published | 26 Nov 2018 |
Publication status | Published - 28 Mar 2019 |
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Link to Scopus | https://www.scopus.com/record/display.uri?eid=2-s2.0-85057308199&origin=recordpage |
Permanent Link | https://scholars.cityu.edu.hk/en/publications/publication(008bc698-ca6e-4fed-8ee2-31ebfe65db4e).html |
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.
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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 et al.
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 journal › peer-review
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