Sodium Butyrate Upregulates MiR-203 Expression To Exert Anti-proliferation Effect On Colorectal Cancer Cells

Background and ObjectivesAs the end product of the bacterial fermentation of dietary fiber in the colonic lumen,sodium butyrate(NaBt)has been reported to exert antitumor effects on colorectal cancer(CRC).In addition to functioning as a histone deacetylase(HDAC)inhibitor,NaBt also regulates the expression of microRNAs(miRNAs)to inhibit CRC cell proliferation.Yet,the mechanisms involved are not completely understood.Here we investigate whether NaBt regulates miR-203 to inhibit CRC growth and explore the promising target gene of miR-203 in CRC cells.MethodsWe conducted qRT-PCR and Western blotting assays to evaluate the effects of Na Bt on the expression of miR-203 and NEDD9 in HT-29 and Caco-2 cell lines.The promising target gene of miR-203 was predicted by miRNA target prediction and dual luciferase reporter assay.CRC Cell proliferation,colony formation,cell apoptosis and cell invasion assays were performed to explore the effect of NaBt,miR-203 and NEDD9 on HT-29 and Caco-2 cell lines.Results1.NaBt upregulates miR-203 and downregulates NEDD9 in HT-29 and Caco-2 cells.2.miR-203 directly targets NEDD9.3.Upregulation of miR-203 inhibits CRC cell proliferation,colony formation and cell invasion as well as induce CRC cell apoptosis.4.NaBt presents similar trends in affecting CRC cell proliferation,colony formation,cell apoptosis and invasion with miR-203 upregulation and NEDD9 knockdown.5.Overexpression of NEDD9 lacking 3'UTR partly reverses the inhibitory effects of miR-203 and NaBt on CRC cells.ConclusionsNaBt could induce CRC cell apoptosis,inhibit CRC cell proliferation,colony formation and invasion through miR-203/NEDD9 cascade.The present study may enrich the mechanisms underlying the process that NaBt exerts anti-tumor effects on CRC cells.