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

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 canc...

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Detalles Bibliográficos
Autores: Bu, Pengcheng, Wang, Lihua, Chen, Kai-Yuan, Rakhilin, Nikolai, Sun, Jian, Closa, Adrià, 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 Aguado, Víctor, Gümüş, Zeynep H., Shen, Xiling
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2015
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/125584
Acceso en línea:https://hdl.handle.net/2445/125584
Access Level:acceso abierto
Palabra clave:Càncer
Quimioteràpia del càncer
Metàstasi
Cancer
Cancer chemotherapy
Metastasis
Descripción
Sumario: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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