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miR-509-3p is clinically significant and strongly attenuates cellular migration and multi-cellular spheroids in ovarian cancer.
Pan, Yinghong; Robertson, Gordon; Pedersen, Lykke; Lim, Emilia; Hernandez-Herrera, Anadulce; Rowat, Amy C; Patil, Sagar L; Chan, Clara K; Wen, Yunfei; Zhang, Xinna; Basu-Roy, Upal; Mansukhani, Alka; Chu, Andy; Sipahimalani, Payal; Bowlby, Reanne; Brooks, Denise; Thiessen, Nina; Coarfa, Cristian; Ma, Yussanne; Moore, Richard A; Schein, Jacquie E; Mungall, Andrew J; Liu, Jinsong; Pecot, Chad V; Sood, Anil K; Jones, Steven J M; Marra, Marco A; Gunaratne, Preethi H.
Afiliação
  • Pan Y; Department of Biochemistry and Biology, University of Houston, Houston, TX, USA.
  • Robertson G; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, Canada.
  • Pedersen L; Department of Biology, University of Copenhagen, Copenhagen, Denmark.
  • Lim E; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, Canada.
  • Hernandez-Herrera A; Department of Biochemistry and Biology, University of Houston, Houston, TX, USA.
  • Rowat AC; Department of Integrative Biology and Physiology, University of California, Los Angeles, CA, USA.
  • Patil SL; Department of Biochemistry and Biology, University of Houston, Houston, TX, USA.
  • Chan CK; Department of Integrative Biology and Physiology, University of California, Los Angeles, CA, USA.
  • Wen Y; Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Zhang X; Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Basu-Roy U; Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Mansukhani A; Department of Microbiology, New York University School of Medicine, New York, NY, USA.
  • Chu A; Department of Microbiology, New York University School of Medicine, New York, NY, USA.
  • Sipahimalani P; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, Canada.
  • Bowlby R; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, Canada.
  • Brooks D; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, Canada.
  • Thiessen N; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, Canada.
  • Coarfa C; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, Canada.
  • Ma Y; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
  • Moore RA; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, Canada.
  • Schein JE; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, Canada.
  • Mungall AJ; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, Canada.
  • Liu J; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, Canada.
  • Pecot CV; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Sood AK; UNC Lineberger Comprehensive Cancer Center, Thoracic Medical Oncology, University of North Carolina, Chapel Hill, NC, USA.
  • Jones SJ; Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Marra MA; Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Gunaratne PH; Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Oncotarget ; 7(18): 25930-48, 2016 May 03.
Article em En | MEDLINE | ID: mdl-27036018
ABSTRACT
Ovarian cancer presents as an aggressive, advanced stage cancer with widespread metastases that depend primarily on multicellular spheroids in the peritoneal fluid. To identify new druggable pathways related to metastatic progression and spheroid formation, we integrated microRNA and mRNA sequencing data from 293 tumors from The Cancer Genome Atlas (TCGA) ovarian cancer cohort. We identified miR-509-3p as a clinically significant microRNA that is more abundant in patients with favorable survival in both the TCGA cohort (P = 2.3E-3), and, by in situ hybridization (ISH), in an independent cohort of 157 tumors (P < 1.0E-3). We found that miR-509-3p attenuated migration and disrupted multi-cellular spheroids in HEYA8, OVCAR8, SKOV3, OVCAR3, OVCAR4 and OVCAR5 cell lines. Consistent with disrupted spheroid formation, in TCGA data miR-509-3p's most strongly anti-correlated predicted targets were enriched in components of the extracellular matrix (ECM). We validated the Hippo pathway effector YAP1 as a direct miR-509-3p target. We showed that siRNA to YAP1 replicated 90% of miR-509-3p-mediated migration attenuation in OVCAR8, which contained high levels of YAP1 protein, but not in the other cell lines, in which levels of this protein were moderate to low. Our data suggest that the miR-509-3p/YAP1 axis may be a new druggable target in cancers with high YAP1, and we propose that therapeutically targeting the miR-509-3p/YAP1/ECM axis may disrupt early steps in multi-cellular spheroid formation, and so inhibit metastasis in epithelial ovarian cancer and potentially in other cancers.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Regulação Neoplásica da Expressão Gênica / Movimento Celular / Neoplasias Epiteliais e Glandulares / MicroRNAs Tipo de estudo: Prognostic_studies Limite: Female / Humans Idioma: En Revista: Oncotarget Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Regulação Neoplásica da Expressão Gênica / Movimento Celular / Neoplasias Epiteliais e Glandulares / MicroRNAs Tipo de estudo: Prognostic_studies Limite: Female / Humans Idioma: En Revista: Oncotarget Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Estados Unidos