Integrated Analyses Identify a Master MicroRNA Regulatory Network for the Mesenchymal Subtype in Serous Ovarian Cancer

被引：354

作者：

Yang, Da ^{[1
]}

Sun, Yan ^{[1
,7
]}

Hu, Limei ^{[1
]}

Zheng, Hong ^{[8
]}

Ji, Ping ^{[1
]}

Pecot, Chad V. ^{[6
]}

Zhao, Yanrui ^{[8
]}

Reynolds, Sheila ^{[9
]}

Chen, Hanyin ^{[1
]}

Rupaimoole, Rajesha ^{[2
]}

Cogdell, David ^{[1
]}

Nykter, Matti ^{[10
]}

Broaddus, Russell ^{[1
]}

Rodriguez-Aguayo, Cristian ^{[4
]}

Lopez-Berestein, Gabriel ^{[4
,5
]}

Liu, Jinsong ^{[1
]}

Shmulevich, Ilya ^{[9
]}

Sood, Anil K. ^{[2
,3
,5
]}

Chen, Kexin ^{[8
]}

Zhang, Wei ^{[1
,5
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA

[2] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol & Reprod Med, Houston, TX 77030 USA

[3] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA

[4] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA

[5] Univ Texas MD Anderson Canc Ctr, Ctr RNAi & Noncoding RNA, Houston, TX 77030 USA

[6] Univ Texas MD Anderson Canc Ctr, Div Canc Med, Houston, TX 77030 USA

[7] Tianjin Med Univ Canc Inst & Hosp, Dept Pathol, Tianjin 300060, Peoples R China

[8] Tianjin Med Univ Canc Inst & Hosp, Dept Epidemiol & Biostat, Tianjin 300060, Peoples R China

[9] Inst Syst Biol, Seattle, WA 98103 USA

[10] Tampere Univ Technol, FIN-33101 Tampere, Finland

来源：

CANCER CELL | 2013年 / 23卷 / 02期

基金：

中国国家自然科学基金; 美国国家卫生研究院;

关键词：

LUNG-CANCER; EPITHELIAL PHENOTYPE; MIR-200; FAMILY; CELLS; GENE; METASTASIS; STATISTICS; TRANSITION; EXPRESSION; CHALLENGES;

D O I：

10.1016/j.ccr.2012.12.020

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 TGF beta-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.

引用

页码：186 / 199

页数：14

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