Integrative network biology analysis identifies miR-508-3p as the determinant for the mesenchymal identity and a strong prognostic biomarker of ovarian cancer
Integrative network biology analysis identifies miR-508-3p as the determinant for the mesenchymal identity and a strong prognostic biomarker of ovarian cancer
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综合网络生物学分析确定 miR-508-3p 是间充质特性的决定因素和卵巢癌的强预后生物标志物
DOI：
10.1038/s41388-018-0577-5
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发表时间：
2018-11
期刊：
影响因子：
8
通讯作者：
Xin Wang
中科院分区：
文献类型：
--
作者：
Linjie Zhao;Wei Wang;Lian Xu;Tao Yi;Xia Zhao;Yuquan Wei;Louis Vermeulen;Ajay Goel;Shengtao Zhou;Xin Wang
卵巢癌是一种异质性恶性肿瘤，具有巨大的临床挑战性。基于全基因组基因表达谱的无监督分类，最近确定了卵巢癌的四种分子亚型。然而，这些亚型特异性的单驱动分子事件尚未明确阐明。我们的目标是利用系统生物学的方法来描述卵巢癌预后不良的间充质亚型的调节机制，包括各种分子模式，包括基因和microRNA表达谱。miR-508-3p是调节间质亚型中一系列失调基因的最强大的决定因素，包括参与上皮-间质转化（EMT）程序的核心基因。此外，启动子高甲基化导致的miR-508-3p下调与体内和体外转移行为直接相关。综上所述，我们的多维网络分析确定了miR-508-3p是一个主要的调节因子，它定义了间质亚型，并提供了一种新的预后生物标志物来改善这种疾病的管理。
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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DOI：
10.1016/b978-0-12-809633-8.20106-4
发表时间：
2020-02
期刊：
--
影响因子：
--
作者：
A. Prjibelski;Anton I. Korobeynikov;Alla L. Lapidus
通讯作者：
A. Prjibelski;Anton I. Korobeynikov;Alla L. Lapidus
影响因子：
14.9
作者：
Ritchie ME;Phipson B;Wu D;Hu Y;Law CW;Shi W;Smyth GK
通讯作者：
Smyth GK
影响因子：
4.7
作者：
Bilyk O;Coatham M;Jewer M;Postovit LM
通讯作者：
Postovit LM
影响因子：
11.1
作者：
Tan, Tuan Zea;Miow, Qing Hao;Huang, Ruby Yun-Ju;Wong, Meng Kang;Ye, Jieru;Lau, Jieying Amelia;Wu, Meng Chu;Hadi, Luqman Hakim Bin Abdul;Soong, Richie;Choolani, Mahesh;Davidson, Ben;Nesland, Jahn M.;Wang, Ling-Zhi;Matsumura, Noriomi;Mandai, Masaki;Konishi, Ikuo;Goh, Boon-Cher;Chang, Jeffrey T.;Thiery, Jean Paul;Mori, Seiichi
通讯作者：
Mori, Seiichi
DOI：
10.1534/g3.116.033514
发表时间：
2016-12-07
期刊：
G3 (Bethesda, Md.)
影响因子：
--
作者：
Way GP;Rudd J;Wang C;Hamidi H;Fridley BL;Konecny GE;Goode EL;Greene CS;Doherty JA
通讯作者：
Doherty JA