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 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.
Bu, P; Wang, L; Chen, K-Y; Rakhilin, N; Sun, J; Closa, A; Tung, K-L; King, S; Kristine Varanko, A; Xu, Y; Huan Chen, J; Zessin, AS; Shealy, J; Cummings, B; Hsu, D; Lipkin, SM; Moreno, V; Gümüş, ZH; Shen, X
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