Sodium Butyrate Inhibits Colorectal Cancer Cell Migration By Downregulating Bmi-1 Through Enhanced MiR-200c Expression

Background and objective:Short chain fatty acid sodium butyrate(NaB)is the byproduct of bacterial anaero-bic fermentation of dietary fiber in the colon,and has been shown antitumor effect on colorectal cancer(CRC).Yet,the mechanisms involved are not completely understood.The miR-200s are key regulators of the epithelial-mesenchymal transition(EMT).Herein,we investigated whether its effect on colorectal cancer cell migration is related to regulating miR-200s expression.Methods and results:HCT116 and LOVO CRC cells were treated with NaB.NaB inhibited CRC cells growth,induced apoptosis and cell cycle arrest in G2 phase.The results of wound heal-ing,transwell assays and spheroid culture showed that NaB inhibited cell migration and invasion while regulating EMT related proteins expression.NaB markedly increased miR-200 family numbers expression and inhibited miR-200 targeted genes(Bmi-1,Zeb1,EZH2)expression.Cells transfected with mir-200c shRNA displayed significant blockage of NaB-induced anti-invasive activity.Overexpression Bmi-1 partially coun-teracts the effect of NaB.Besides,NaB inhibited tumor growth in vivo.qRT-PCR results showed that NaB increased miR-200c/200b/492,but not miR-200a/141 expression in tumor tissues.IHC and Western blotting assays results showed that NaB decreased Bmi-1 expression in vivo.Conclusion:NaB inhibits CRC cell migration by enhancing miR-200c expression mediated downregulation of Bmi-1.These findings support the utility of NaB in CRC therapy.