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

Abstract

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.

Long noncoding RNA HCG18 up‐regulates the expression of WIPF1 and YAP/TAZ by inhibiting miR‐141‐3p in gastric cancer

“…26 In GC, miRNAs have been found to play various regulatory roles in cell PLF, MGT, multidrug resistance, etc For example, miR-4268 represses the PLF of GC cells by targeting Rab6B 27 ; miR-107 modulates the growth and MGT of GC cells by down-regulating FAT4 to activate PI3K-AKT signaling pathway 28 ; miR-200c reverses the cisplatin resistance of GC by targeting NER-ERCC3/4. 29 Reportedly, miR-141-3p expression is down-regulated in multiple tumors. For example, miR-141-3p expression is decreased in CRC, and miR-141-3p high expression can inhibit cell PLF and MGT.…”

Noncoding RNAs in gastric cancer: implications for drug resistance

“…MiRNAs are a class of sncRNAs of 19-24 nt in length, which could post-transcriptionally suppress gene expression via binding to the 3'-untranslated region (3'-UTR) of multiple target messenger RNAs (mRNAs) and/or other RNAs [42,43]. Multiple miRNAs are dysregulated in gastric cancer and play a crucial role in tumorigenesis, cancer metastasis, as well as development of resistance to drugs and radiation [44][45][46][47][48]. It has been observed that significantly changed miRNA expression profiles in drug-resistant gastric cancer cells compared to those in drug-sensitive cells.…”

MicroRNA-200b reduced ZEB1 to inhibit cell proliferation and migration in human gastric cancer

“…On the other hand, accumulating evidence strongly suggests that miR-200c could reverse drug resistance of GC. [9]. The miR-200 family members (miR-200a, miR-200b, miR-200c, miR-141, and miR-429) [10] could inhibite epithelial-mesenchymal transition (EMT) by targeting E-cadherin, ZEB1 or ZEB2 [11].…”