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miR-1269 promotes metastasis and forms a positive feedback loop with TGF-ß.
Bu, Pengcheng; Wang, Lihua; Chen, Kai-Yuan; Rakhilin, Nikolai; Sun, Jian; Closa, Adria; Tung, Kuei-Ling; King, Sarah; Kristine Varanko, Anastasia; Xu, Yitian; Huan Chen, Joyce; Zessin, Amelia S; Shealy, James; Cummings, Bethany; Hsu, David; Lipkin, Steven M; Moreno, Victor; Gümüs, Zeynep H; Shen, Xiling.
Afiliação
  • Bu P; 1] School of Electrical and Computer Engineering, Cornell University, Ithaca, New York 14853, USA [2] Department of Biomedical Engineering, Cornell University, Ithaca, New York 14853, USA.
  • Wang L; Department of Biological and Environmental Engineering, Cornell University, Ithaca, New York 14853, USA.
  • Chen KY; School of Electrical and Computer Engineering, Cornell University, Ithaca, New York 14853, USA.
  • Rakhilin N; School of Electrical and Computer Engineering, Cornell University, Ithaca, New York 14853, USA.
  • Sun J; 1] Departments of Medicine, Genetic Medicine and Surgery, Weill Cornell Medical College, New York, New York 10021, USA [2] Department of Physiology and Biophysics, Weill Cornell Medical College, New York, New York 10021, USA.
  • Closa A; 1] Department of Clinical Sciences, University of Barcelona, Barcelona 08193, Spain [2] Cancer Prevention and Control Program, Catalan Institute of Oncology-IDIBELL, CIBERESP, Barcelona E08907, Spain.
  • Tung KL; Department of Biological and Environmental Engineering, Cornell University, Ithaca, New York 14853, USA.
  • King S; Department of Biological and Environmental Engineering, Cornell University, Ithaca, New York 14853, USA.
  • Kristine Varanko A; Department of Biological and Environmental Engineering, Cornell University, Ithaca, New York 14853, USA.
  • Xu Y; Department of Biological and Environmental Engineering, Cornell University, Ithaca, New York 14853, USA.
  • Huan Chen J; Department of Biomedical Engineering, Cornell University, Ithaca, New York 14853, USA.
  • Zessin AS; Division of Medical Oncology, Duke Cancer Institute, Duke University, Durham, North Carolina 27710, USA.
  • Shealy J; School of Electrical and Computer Engineering, Cornell University, Ithaca, New York 14853, USA.
  • Cummings B; Department of Biomedical Sciences, Cornell University, Ithaca, New York 14853, USA.
  • Hsu D; Division of Medical Oncology, Duke Cancer Institute, Duke University, Durham, North Carolina 27710, USA.
  • Lipkin SM; Departments of Medicine, Genetic Medicine and Surgery, Weill Cornell Medical College, New York, New York 10021, USA.
  • Moreno V; 1] Department of Clinical Sciences, University of Barcelona, Barcelona 08193, Spain [2] Cancer Prevention and Control Program, Catalan Institute of Oncology-IDIBELL, CIBERESP, Barcelona E08907, Spain.
  • Gümüs ZH; 1] Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10065, USA [2] Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York 10065, USA.
  • Shen X; 1] School of Electrical and Computer Engineering, Cornell University, Ithaca, New York 14853, USA [2] Department of Biomedical Engineering, Cornell University, Ithaca, New York 14853, USA [3] Department of Biological and Environmental Engineering, Cornell University, Ithaca, New York 14853, USA.
Nat Commun ; 6: 6879, 2015 Apr 15.
Article em En | MEDLINE | ID: mdl-25872451
ABSTRACT
As patient survival drops precipitously from early-stage cancers to late-stage and metastatic cancers, microRNAs that promote relapse and metastasis can serve as prognostic and predictive markers as well as therapeutic targets for chemoprevention. Here we show that miR-1269a promotes colorectal cancer (CRC) metastasis and forms a positive feedback loop with TGF-ß signalling. miR-1269a is upregulated in late-stage CRCs, and long-term monitoring of 100 stage II CRC patients revealed that miR-1269a expression in their surgically removed primary tumours is strongly associated with risk of CRC relapse and metastasis. Consistent with clinical observations, miR-1269a significantly increases the ability of CRC cells to invade and metastasize in vivo. TGF-ß activates miR-1269 via Sox4, while miR-1269a enhances TGF-ß signalling by targeting Smad7 and HOXD10, hence forming a positive feedback loop. Our findings suggest that miR-1269a is a potential marker to inform adjuvant chemotherapy decisions for CRC patients and a potential therapeutic target to deter metastasis.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Colorretais / Fator de Crescimento Transformador beta / Retroalimentação Fisiológica / MicroRNAs / Recidiva Local de Neoplasia Tipo de estudo: Prognostic_studies Limite: Aged80 Idioma: En Revista: Nat Commun Ano de publicação: 2015 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Colorretais / Fator de Crescimento Transformador beta / Retroalimentação Fisiológica / MicroRNAs / Recidiva Local de Neoplasia Tipo de estudo: Prognostic_studies Limite: Aged80 Idioma: En Revista: Nat Commun Ano de publicação: 2015 Tipo de documento: Article