期刊
ONCOGENE
卷 38, 期 13, 页码 2305-2319出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41388-018-0577-5
关键词
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资金
- National Natural Science Foundation of China [81822034, 81773119, 81402396]
- National Key Research and Development Program of China [2018YFA0109200, 2017YFA0106800]
- Sichuan Science-Technology Soft Sciences Project [2016ZR0086]
- West China Second Hospital, Sichuan University [KS021]
- Research Grants Council of the Hong Kong Special Administrative Region, China [CityU 21101115, 11102317, 11103718]
- Science Technology and Innovation Committee of Shenzhen Municipality [JCYJ20170307091256048]
- Shenzhen Research Institute, City University of Hong Kong
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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