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.