Resveratrol restrains colorectal cancer metastasis by regulating miR-125b-5p/TRAF6 signaling axis

Colorectal Cancer is one of the most common malignancies with a high incidence, metastatic tendency and low 5-year survival rate. Resveratrol, a polyphenolic compound has been shown to inhibit colorectal Cancer metastasis in recent studies. Its underlying molecular mechanism remains to be elucidated. Our findings demonstrated that miR-125b-5p, acting as a tumor suppressor, was conspicuously down-regulated in both colorectal Cancer tissues and cell lines. The expression of miR-125b-5p negatively correlated with the expression of its direct target TNF Receptor associated factor 6 (TRAF6). Both miR-125b-5p overexpression and TRAF6 knockdown inhibited metastasis of colorectal Cancer cells. In addition, we uncovered that resveratrol up-regulated miR-125b-5p by increasing its stability and suppressed TRAF6-induced signal pathway in a dose/time-dependent manner. Resveratrol could significantly curtail the migration and invasion of colorectal Cancer cells, which was counteracted by miR-125b-5p knockdown or TRAF6 overexpression. These results indicated that resveratrol could restrain colorectal Cancer metastasis by promoting miR-125b-5p/TRAF6 signaling axis. Furthermore, lung metastasis models of colorectal Cancer were constructed by tail vein injection. Down-regulation of miR-125b-5p could facilitate colorectal Cancer metastasis in vivo, which could be impeded by resveratrol. In conclusion, our findings delineated the miR-125b-5p/TRAF6 signaling axis as a novel molecular mechanism underlying the metastatic process in colorectal Cancer, as well as a prospective therapeutic target. Resveratrol disrupts colorectal Cancer metastasis by activating miR-125b-5p/TRAF6 signal pathway and might improve the clinical outcome of colorectal Cancer patients with low expression of miR-125b-5p.

Resveratrol; TRAF6; colorectal cancer; metastasis; miR-125b-5p.