MiR-192-5p Reverses Cisplatin Resistance Of Gastric Cancer Cell Lines By Targeting ERCC3 And ERCC4 In Vivo

Objective In order to explore whether miR-192-5p can reverse cisplatin resistance in nude mice subcutaneously transplanted gastric cancer cells SGC7901 by regulate nucleotide excision repair(NER)protein ERCC3 and ERCC4 in vivo.Methods We used microarray system to analyze the lncRNA,mRNA and miRNA expression in SGC7901/DDP cells compared with SGC7901 lines.Bioinformatics analysis software was used to predicte the target of miR-192-5p.Lentivirus with interference fragment were used to upregulated miR-192-5p in SGC7901/DDP cells and downregulated miR-192-5p in SGC7901 cells.Quantitative real-time PCR assays were used to measure the expression of miR-192-5p.Western blot was used to evaluate the proteins of ERCC3 and ERCC4 after lentiviral transfection.IC50 of cells were assessed by MTT assays to evaluation of cells to cisplatin resistance in vitro.Then cells were injected into subcutaneous of BALB/C nude mice and then given cisplatin by intraperitoneal perfusion for test cisplatin resistance after upregulated and downregulated miR-192-5p in vivo.Results Microarray analysis showed that the significantly dysregulated lncRNA,mRNA and miRNA may be associated with cisplatin resistance in gatric cancer cells.The expression of miR-192-5p is downregulated in SGC7901/DDP cells,however the mRNA of ERCC3 and ERCC4 were upregulated in SGC7901/DDP.The analysis of bioinformatics software showed that ERCC3 and ERCC4 were the direct target genes of miR-192-5p.Ectopic expression of miR-192-5p in SGC7901/DDP cells dramatically decreased the expression of ERCC3 /ERCC4 and reversed cisplatin resistance in vivo and in vitro.Conversely,transfection of miR-192-5p inhibitor in SGC7901 cells could increase ERCC3 and ERCC4 level and enhanced cisplatin resistance in vivo and in vitro.Conclusions Taken together,our findings suggested that miR-192-5p could reverse cisplatin resistance by targeting ERCC3 and ERCC4 in vitro and in vivo,which potentially contributed to GC chemo-resistance.