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

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, James Shealy, Bethany Cummings, David Hsu, Steven M. Lipkin, Victor Moreno, Zeynep H. Gümüş and Xiling Shen ()
Additional contact information
Pengcheng Bu: School of Electrical and Computer Engineering, 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
Adria Closa: University of Barcelona
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
Zeynep H. Gümüş: Icahn School of Medicine at Mount Sinai
Xiling Shen: School of Electrical and Computer Engineering, Cornell University

Nature Communications, 2015, vol. 6, issue 1, 1-12

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms7879

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