Bu, PengchengWang, LihuaChen, Kai-YuanRakhilin, NikolaiSun, JianClosa, AdriàTung, Kuei-LingKing, SarahKristine Varanko, AnastasiaXu, YitianHuan Chen, JoyceZessin, Amelia S.Shealy, JamesCummings, BethanyHsu, DavidLipkin, Steven M.Moreno Aguado, VíctorGümüş, Zeynep H.Shen, Xiling2018-10-242018-10-242015-04-152041-1723https://hdl.handle.net/2445/125584As 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.application/pdfengcc-by (c) Bu, Pengcheng et al., 2015http://creativecommons.org/licenses/by/3.0/esCàncerQuimioteràpia del càncerMetàstasiCancerCancer chemotherapyMetastasisinfo:eu-repo/semantics/article6602052018-10-24info:eu-repo/semantics/openAccess25872451