MicroRNA-200c reverses drug resistance of human gastric cancer cells by targeting regulation of the NER-ERCC3/4 pathway.

Gastric cancer (GC) is one of the most common types of malignant tumor. Due to the lack of effective drugs and the emergence of chemotherapy resistance, patients with GC exhibit a poor prognosis and low survival rate. MicroRNAs (miRNAs/miRs) serve an important role in drug resistance of different types of cancer. They may be suitable for use as biomarkers in the diagnosis, treatment and prognosis of tumors. The present study aimed to investigate the molecular mechanism underlying the ability of miR-200c-3p to reverse drug resistance in a SGC7901/DDP GC cell line, particularly its effects on the ERCC excision repair 3, TFIIH core complex helicase subunit (ERCC3) and ERCC excision repair 4, endonuclease catalytic subunit (ERCC4) proteins in the nucleotide excision repair (NER) pathway. Reverse transcription-quantitative polymerase chain reaction demonstrated that miR-200c-3p expression in cisplatin-resistant SGC7901/DDP cells was lower than in parental SGC7901 cells, whereas the protein expression levels of ERCC3 and ERCC4 in these cells were higher by western blot analysis. In SGC7901/DDP-derived miR-200c-3p overexpressing cells, ERCC3 expression, ERCC4 expression and cisplatin resistance were decreased compared with in parental SGC7901/DDP cells and SGC7901/DDP-derived vector control cells. In SGC7901-derived miR-200c-3p knockdown cells, ERCC3 expression, ERCC4 expression and cisplatin resistance were increased compared with in parental SGC7901 cells and SGC7901-derived vector control cells. In conclusion, overexpression of miR-200c-3p may reverse drug resistance in the SGC7901/DDP GC cell line via downregulation of ERCC3 and ERCC4, which suggested this may be part of a mechanism involving the NER pathway.