title: Integrated analyses identify a master microRNA regulatory network for the mesenchymal subtype in serous ovarian cancer.
abstract: 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.
authors: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Da
authors: D
authors: Yang
authors: Yan
authors: Y
authors: Sun
authors: Limei
authors: L
authors: Hu
authors: Hong
authors: H
authors: Zheng
authors: Ping
authors: P
authors: Ji
authors: Chad V
authors: CV
authors: Pecot
authors: Yanrui
authors: Y
authors: Zhao
authors: Sheila
authors: S
authors: Reynolds
authors: Hanyin
authors: H
authors: Cheng
authors: Rajesha
authors: R
authors: Rupaimoole
authors: David
authors: D
authors: Cogdell
authors: Matti
authors: M
authors: Nykter
authors: Russell
authors: R
authors: Broaddus
authors: Cristian
authors: C
authors: Rodriguez-Aguayo
authors: Gabriel
authors: G
authors: Lopez-Berestein
authors: Jinsong
authors: J
authors: Liu
authors: Ilya
authors: I
authors: Shmulevich
authors: Anil K
authors: AK
authors: Sood
authors: Kexin
authors: K
authors: Chen
authors: Wei
authors: W
authors: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000235:genetics*; D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects; D018284:Cystadenocarcinoma, Serous / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008648:Mesoderm / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D060787:Neoplasm Grading; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071250:Snail Family Transcription Factors; D015996:Survival Rate; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014746:Vimentin / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; D035683:MicroRNAs; D012333:RNA, Messenger; C000604408:SNAI2 protein, human; C000604449:Snai2 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D014746:Vimentin