Preliminary Study On Interaction Of DNMTs,microRNAs During Early Stage Of Colorectal Carcinogenesis And Mechanism Of Intervention Effect Of Zuojin Pill

ObjectiveTo investigate the characterization of microRNAs、DNMTs(DNA transmethylases) expression profiles,and their interaction in early stage of colorectal carcinogenesis,and exam effect of berberine and evodiamine,which are two main components of Zuojin Pill,on microRNAs and DNMTs.MethodsMicroRNA microarray was used to characterize microRNA expression during early stage of colorectal cancer initiation. To confirm character of DNMTs expression and tissue structure,immunohistochemistry and Western Blot were used. A model was established in which TGF-β was used to induce colorectal carcinogenesis, we examed effect of berberine,evodiamine on both of DNMTs and microRNAs with this model.ResultsProfiling of DNMTs-regulating microRNAs during colorectal carcinogenesis was performed by microRNA microarray. Biological characters including tissue structure,cells,expression of DNMTs and microRNAs were confirmed. Preliminary pharmacological study of berberine,evodiamine on DNMTs and microRNAs was carried on a tissue culture model.ConclusionDNMT1,DNMT3A and DNMT3B were seprately upregulated.MicroRNAs that regulate DNMTs show abberent expression during colorectal carcinogenesis. After treated with5-Aza-dC,expression of DNMTs-regulating microRNAs significantly increased,which means that DNMTs are regulated by microRNAs meanwhile regulating those microRNAs.Berberine and evodiamine had significant influence on expression of DNMTs and microRNA.