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

TitlemiR-1269 promotes metastasis and forms a positive feedback loop with TGF-β.
Publication TypeJournal Article
Year of Publication2015
AuthorsBu, P, Wang, L, Chen, K-Y, Rakhilin, N, Sun, J, Closa, A, Tung, K-L, King, S, A Varanko, Kristine, Xu, Y, J Chen, Huan, Zessin, AS, Shealy, J, Cummings, B, Hsu, D, Lipkin, SM, Moreno, V, Gümüş, ZH, and Shen, X
JournalNature Communications
Volume6
Start Page6879
Date Published04/2015
Abstract

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.

DOI10.1038/ncomms7879
Short TitleNature Communications