TY - JOUR
T1 - Integrated Analyses Identify a Master MicroRNA Regulatory Network for the Mesenchymal Subtype in Serous Ovarian Cancer
AU - Yang, Da
AU - Sun, Yan
AU - Hu, Limei
AU - Zheng, Hong
AU - Ji, Ping
AU - Pecot, Chad V.
AU - Zhao, Yanrui
AU - Reynolds, Sheila
AU - Cheng, Hanyin
AU - Rupaimoole, Rajesha
AU - Cogdell, David
AU - Nykter, Matti
AU - Broaddus, Russell
AU - Rodriguez-Aguayo, Cristian
AU - Lopez-Berestein, Gabriel
AU - Liu, Jinsong
AU - Shmulevich, Ilya
AU - Sood, Anil K.
AU - Chen, Kexin
AU - Zhang, Wei
N1 - Funding Information:
We thank Drs. Xinna Zhang and George Calin for their assistance with miRNA in situ hybridization, Yingmei Wang and Jared Burks (Flow Cytometry & Cellular Imaging Core Facility) for technical assistance, Yuexin Liu for discussion, and Ms. Ann Sutton in the Department of Scientific Publications and Brittany Parker for editing this manuscript. This study was supported by a grant from the National Institutes of Health (U24CA143835) to I.S. and W.Z.; a grant from the Blanton-Davis Ovarian Cancer Research Program to W.Z.; an Ovarian Cancer SPORE grant (P50 CA083639), Ovarian Cancer Research Fund Program Project Development Grant, the Gilder Foundation and U54 CA151668 grant to A.K.S.; the Program for Changjiang Scholars and Innovative Research Team in University (IRT1076) in China and National Key Scientific and Technological Project (2011ZX0 9307-001-04) and Tianjin Science and Technology Committee Foundation grants (09ZCZDSF04700) to K.C.; and the Finnish Funding Agency for Technology and Innovation Finland Distinguished Professor Program to M.N.. The genomic studies were supported in part by the Cancer Genomics Core Laboratory and the National Institutes of Health through The University of Texas MD Anderson’s Cancer Center Support Grant (CA016672). D.Y. is an Odyssey Fellow at MD Anderson Cancer Center, and supported by The Diane Denson Tobola Fellowship in Ovarian Cancer Research fellowship and The Harold C. and Mary L. Daily Endowment Fund. Y.S. is supported by the National Natural Science Foundation of China (81201651), the Linda K. Manning Fellowship in Ovarian Cancer, and The A. Lavoy Moore Endowment Fund.
PY - 2013/2/11
Y1 - 2013/2/11
N2 - Integrated genomic analyses revealed a miRNA-regulatory network that further defined a robust integrated mesenchymal subtype associated with poor overall survival in 459 cases of serous ovarian cancer (OvCa) from The Cancer Genome Atlas and 560 cases from independent cohorts. Eight key miRNAs, including miR-506, miR-141, and miR-200a, were predicted to regulate 89% of the targets in this network. Follow-up functional experiments illustrate that miR-506 augmented E-cadherin expression, inhibited cell migration and invasion, and prevented TGFβ-induced epithelial-mesenchymal transition by targeting SNAI2, a transcriptional repressor of E-cadherin. In human OvCa, miR-506 expression was correlated with decreased SNAI2 and VIM, elevated E-cadherin, and beneficial prognosis. Nanoparticle delivery of miR-506 in orthotopic OvCa mouse models led to E-cadherin induction and reduced tumor growth.
AB - Integrated genomic analyses revealed a miRNA-regulatory network that further defined a robust integrated mesenchymal subtype associated with poor overall survival in 459 cases of serous ovarian cancer (OvCa) from The Cancer Genome Atlas and 560 cases from independent cohorts. Eight key miRNAs, including miR-506, miR-141, and miR-200a, were predicted to regulate 89% of the targets in this network. Follow-up functional experiments illustrate that miR-506 augmented E-cadherin expression, inhibited cell migration and invasion, and prevented TGFβ-induced epithelial-mesenchymal transition by targeting SNAI2, a transcriptional repressor of E-cadherin. In human OvCa, miR-506 expression was correlated with decreased SNAI2 and VIM, elevated E-cadherin, and beneficial prognosis. Nanoparticle delivery of miR-506 in orthotopic OvCa mouse models led to E-cadherin induction and reduced tumor growth.
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U2 - 10.1016/j.ccr.2012.12.020
DO - 10.1016/j.ccr.2012.12.020
M3 - Article
C2 - 23410973
AN - SCOPUS:84873582060
SN - 1535-6108
VL - 23
SP - 186
EP - 199
JO - Cancer cell
JF - Cancer cell
IS - 2
ER -