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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Authors: 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
Format: Article
Status:Published version
Publication date:2015
Country:España
Institution:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repository:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/125584
Online Access:https://hdl.handle.net/2445/125584
Access Level:Open access
Keyword:Càncer
Quimioteràpia del càncer
Metàstasi
Cancer
Cancer chemotherapy
Metastasis
Summary: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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