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


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2019-03

AUTHORS

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

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. More... »

PAGES

2305-2319

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41388-018-0577-5

    DOI

    http://dx.doi.org/10.1038/s41388-018-0577-5

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1110201276

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30478449


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