The Study Of MiR-483-3p Regulates Oxaliplatin Resistance By Targeting FAM171B In Colorectal Cancer

Oxaliplatin is considered to be one of the most effective chemotherapeutic drugs for colorectal cancer(CRC).Howerver,oxaliplatin resistance limits the efficiency of treatment for colorectal cancer(CRC).Studies have shown that abnormal expression of micro RNAs(mi RNAs)were associated with tumorigenesis,cancer development and chemoresistance.The purpose of this study was to identify potential mi RNAs and target genes related to oxaliplatin resistance in CRC cells.To determine the mechanism underlying oxaliplatin resistance,oxaliplatin-resistant cells(HCT116/L)were established based on the parental cells(HCT116).Subsequently,the expression levels of mi RNAs and genes of HCT116 and HCT116/L cell lines were analyzed by small RNA sequencing(small RNA-Seq)and transcriptome sequencing(RNA-Seq)techniques.Sequencing results showed that the number of differentially expressed mi RNAs and genes were 189 and 1671,respectively.In these mi RNAs,we observed that mi R-484-3p may be associated with drug resistance of CRC cells.By combined analysis of small RNA-Seq and RNA-Seq,it was found that the target gene of mi R-483-3p may be FAM171 B.The sequencing results showed that mi R-483-3p was down-regulated in oxaliplatin-resistant cell line HCT116/L as compared with its parental cell line HCT116,while the gene FAM171 B was up-regulated.On the one hand,transient transfection of mi R-483-3p mimics in HCT116/L cells markedly decreased the levels of FAM171 B and restored oxaliplatin responsiveness of HCT116/L cells,and this alteration enhanced cell apoptosis and weakened cell migration.On the other hand,transient transfection of mi R-483-3p inhibitor in HCT116 cells dramatically promoted the expression of FAM171 B and enhanced oxaliplatin resistance of HCT116 cells by repressing cell apoptosis.Furthermore,knockdown of FAM171 B in HCT116/L cellls could also sensitized its reaction of the treatment with oxaliplatin,which was verified by the reduced cell migration.These findings demonstrate that mi R-483-3p regulates oxaliplatin resistance by targeting FAM171 B in human colorectal cancer cells.