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miR-1269 promotes metastasis and forms a positive feedback loop with TGF-β

Author

Listed:
  • Pengcheng Bu

    (School of Electrical and Computer Engineering, Cornell University
    Cornell University)

  • Lihua Wang

    (Cornell University)

  • Kai-Yuan Chen

    (School of Electrical and Computer Engineering, Cornell University)

  • Nikolai Rakhilin

    (School of Electrical and Computer Engineering, Cornell University)

  • Jian Sun

    (Genetic Medicine and Surgery, Weill Cornell Medical College
    Weill Cornell Medical College)

  • Adria Closa

    (University of Barcelona
    Cancer Prevention and Control Program, Catalan Institute of Oncology-IDIBELL, CIBERESP)

  • Kuei-Ling Tung

    (Cornell University)

  • Sarah King

    (Cornell University)

  • Anastasia Kristine Varanko

    (Cornell University)

  • Yitian Xu

    (Cornell University)

  • Joyce Huan Chen

    (Cornell University)

  • Amelia S. Zessin

    (Duke Cancer Institute, Duke University)

  • James Shealy

    (School of Electrical and Computer Engineering, Cornell University)

  • Bethany Cummings

    (Cornell University)

  • David Hsu

    (Duke Cancer Institute, Duke University)

  • Steven M. Lipkin

    (Genetic Medicine and Surgery, Weill Cornell Medical College)

  • Victor Moreno

    (University of Barcelona
    Cancer Prevention and Control Program, Catalan Institute of Oncology-IDIBELL, CIBERESP)

  • Zeynep H. Gümüş

    (Icahn School of Medicine at Mount Sinai
    Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai)

  • Xiling Shen

    (School of Electrical and Computer Engineering, Cornell University
    Cornell University
    Cornell University)

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-β 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-β activates miR-1269 via Sox4, while miR-1269a enhances TGF-β 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.

Suggested Citation

  • Pengcheng Bu & Lihua Wang & Kai-Yuan Chen & Nikolai Rakhilin & Jian Sun & Adria Closa & Kuei-Ling Tung & Sarah King & Anastasia Kristine Varanko & Yitian Xu & Joyce Huan Chen & Amelia S. Zessin & Jame, 2015. "miR-1269 promotes metastasis and forms a positive feedback loop with TGF-β," Nature Communications, Nature, vol. 6(1), pages 1-12, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7879
    DOI: 10.1038/ncomms7879
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