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; Xiling Shen

doi:10.1038/ncomms7879

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, Xiling Shen

Research output: Contribution to journal › Article › peer-review

108 Scopus citations

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.

Original language	English (US)
Article number	6879
Journal	Nature Communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms7879
State	Published - Apr 15 2015

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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Bu, P., Wang, L., Chen, K. Y., Rakhilin, N., Sun, J., Closa, A., Tung, K. L., King, S., Varanko, A. K., Xu, Y., Chen, J. H., Zessin, A. S., Shealy, J., Cummings, B., Hsu, D., Lipkin, S. M., Moreno, V., Gümüş, Z. H., & Shen, X. (2015). miR-1269 promotes metastasis and forms a positive feedback loop with TGF-β. Nature Communications, 6, Article 6879. https://doi.org/10.1038/ncomms7879

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title = "miR-1269 promotes metastasis and forms a positive feedback loop with TGF-β",

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.",

author = "Pengcheng Bu and Lihua Wang and Chen, {Kai Yuan} and Nikolai Rakhilin and Jian Sun and Adria Closa and Tung, {Kuei Ling} and Sarah King and Varanko, {Anastasia Kristine} and Yitian Xu and Chen, {Joyce Huan} and Zessin, {Amelia S.} and James Shealy and Bethany Cummings and David Hsu and Lipkin, {Steven M.} and Victor Moreno and G{\"u}m{\"u}{\c s}, {Zeynep H.} and Xiling Shen",

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AU - Bu, Pengcheng

AU - Wang, Lihua

AU - Chen, Kai Yuan

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AU - Sun, Jian

AU - Closa, Adria

AU - Tung, Kuei Ling

AU - King, Sarah

AU - Varanko, Anastasia Kristine

AU - Xu, Yitian

AU - Chen, Joyce Huan

AU - Zessin, Amelia S.

AU - Shealy, James

AU - Cummings, Bethany

AU - Hsu, David

AU - Lipkin, Steven M.

AU - Moreno, Victor

AU - Gümüş, Zeynep H.

AU - Shen, Xiling

PY - 2015/4/15

Y1 - 2015/4/15

N2 - 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.

AB - 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.

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

Abstract

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