|Title||miR-1269 promotes metastasis and forms a positive feedback loop with TGF-β.|
|Publication Type||Journal Article|
|Year of Publication||2015|
|Authors||Bu, P, L Wang, K-Y Chen, N Rakhilin, J Sun, A Closa, K-L Tung, S King, Kristine A Varanko, Y Xu, Huan J Chen, AS Zessin, J Shealy, B Cummings, D Hsu, SM Lipkin, V Moreno, ZH Gümüş, and X Shen|
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.
|Short Title||Nature Communications|