Cisplatin chemoresistance is a clinical obstacle in the treatment of gastric cancer (GC). Enhanced DNA repair capacity may lead to cisplatin resistance. However, the detailed molecular mechanism of GC cisplatin resistance specifically involving nucleotide excision repair (NER) is not clear. However, the mechanism through which the NER pathway contributes to cisplatin resistance in GC is still unclear. In light of the crucial role of microRNAs (miRNAs) in regulating protein expression and biological behavior, we aimed to analyze the expression and function of miR-192-5p in the NER pathway and its role in cisplatin resistance in GC. Comet assays were performed to measure the amount of DNA damage and repair in the SGC7901 and SGC7901/DDP GC cell lines by observing the tail length. MiRNA expression levels in SGC7901/DDP and SGC7901 cells were detected by microarray. Quantitative real-time PCR (qRT-PCR) was carried out to confirm the expression level of miR-192-5p. Lentiviral vector transfection modifies miR-192-5p levels in SGC7901/DDP and SGC7901 cells. The IC 50 values of cisplatin-treated cells were assessed by MTT assays. The protein level was determined by Western blot and immunohistochemistry. With enhanced DNA repair, the expression levels of ERCC3 and ERCC4 in SGC 7901DDP cells increased, while miR-192-5p was significantly downregulated in SGC7901/DDP compared with SGC7901 cells. ERCC3 and ERCC4 were identified as the main targets of miR-192-5p. Forced expression of miR-192-5p in SGC7901/DDP cells significantly inhibited the expression of ERCC3 and ERCC4, making GC cells more sensitive to cisplatin in vitro and in vivo. In contrast, knockdown of miR-192-5p expression in SGC7901 cells increased the expression of ERCC3 and ERCC4, resulting in cisplatin resistance in vitro and in vivo. MiR-192-5p partially reversed GC cisplatin resistance by targeting ERCC3 and ERCC4, which participate in the NER pathway, suggesting that miR-192-5p may be a potential biomarker and therapeutic target for GC cisplatin resistance.

The microRNA (miR)-138-5p affects the chemotherapeutic sensitivity of several human cancer types. In the present study, the expression and regulatory mechanisms of miR-138-5p were investigated in the gastric cancer cell line SGC7901 and its cisplatin-resistant derivative SGC7901/DDP. Gene microarray and reverse transcription-quantitative polymerase chain reaction analyses revealed that miR-138-5p was expressed at significantly lower levels in SGC7901/DDP compared with SGC7901 cells. Using computational predictive algorithms, two proteins involved in the nuclear excision repair pathway were identified, excision repair cross-complementing (ERCC)1 and ERCC4, as putative miR-138-5p target genes. Western blot analysis confirmed that ERCC1 and ERCC4 expression levels were inversely proportional to miR-138-5p levels in SGC7901 and SGC7901/DDP cells. Furthermore, ERCC1 and ERCC4 were upregulated in SGC7901 cells expressing miR-138-5p-targeting short hairpin RNA and, conversely, downregulated in SGC7901/DDP cells overexpressing miR-138-5p, confirming that this miRNA regulates ERCC protein levels. Notably, miR-138-5p silencing enhanced the cisplatin resistance of SGC7901 cells, while miR-138-5p overexpression partially reversed the cisplatin resistance of SGC7901/DDP cells. Taken together, these data suggest that miR-138-5p regulates the sensitivity of gastric cancer cells to cisplatin, possibly by modulating expression of the DNA repair proteins ERCC1 and ERCC4.

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.

We examined microRNA-200c (miR-200c) expression in tumor tissues and plasma of patients with advanced gastric cancer and correlated miR-200c expression with treatment efficacy of platinum chemotherapy and patient prognosis. Tumor tissues were collected from 51 patients with advanced gastric cancer who received platinum-containing chemotherapies. The plasma was collected from the same group of patients and 51 subjects with chronic superficial gastritis. Quantitative RT-PCR was used to evaluate miR-200c expression, and its correlation with treatment efficacy and patient prognosis was analyzed.The results showed that the miR-200c expression in gastric cancer tissues and in plasma were significantly lower than tumor-adjacent tissues and in patients with chronic superficial gastritis (both p <0.05). No significant correlation was found between miR-200c expression in tumors or plasma and clinical characteristics. Patients with higher miR-200c expression had better treatment outcomes with platinum chemotherapy and longer progression-free survival and overall survival than patients with lower miR-200c expression. Receiver-operating characteristic curve analysis showed that miR-200c expression in gastric cancer tissues and plasma distinguished patients’ treatment outcomes. Multivariate analyses confirmed that over expression of miR-200c both in gastric cancer tissue and plasma is associated with longer progression-free survival and overall survival. Taken together, our study indicated that miR-200c expression in gastric cancer tissues and plasma of patients with advanced gastric cancer is associated with better treatment efficacy and prognosis with platinum chemotherapy, suggesting that expression of miR-200c may be predictive for chemotherapy and prognosis in advanced gastric cancer patients.

Chemotherapy resistance is a major obstacle to the effective treatment of patients with gastric cancer (GC). Mounting evidence has indicated that the dysregulation of microRNAs (miRNAs) is associated with the sensitivity of cancer cells to chemotherapy. However, the mechanisms underlying miRNA-mediated chemoresistance in GC cells remain to be elucidated. The present study aimed to identify functional miRNAs that may regulate the sensitivity of human GC cells to cisplatin (DDP) treatment. miRNA microarray analysis was used to identify differentially expressed miRNAs between the human cisplatin-sensitive GC cell line SGC7901 and the corresponding cisplatin-resistant cell line SGC7901/DDP. miRNA (miR)-362-5p, which is associated with numerous types of tumors, was identified to be downregulated in the SGC7901/DDP cell line. However, the biological role of miR-362-5p in SGC7901/DDP cells remains to be explored. The expression level of miR-362-5p was demonstrated to be reduced in SGC7901/DDP cells compared with SGC7901 cells by reverse transcription-quantitative PCR. Upregulation of miR-362-5p significantly increased cisplatin sensitivity and cisplatin-induced apoptosis, whereas downregulation of miR-362-5p attenuated these effects. Databases predicted that suppressor of zeste 12 protein (SUZ12) may function as a target of miR-362-5p. In addition, the mRNA and protein expression levels of SUZ12 in SGC7901/DDP cells were significantly higher compared with SGC7901 cells and negatively associated with miR-362-5p expression. MTT and western blot analysis assays confirmed that knockdown of SUZ12 enhanced cisplatin sensitivity and decreased NF-κB/p65 protein levels in SGC7901/DDP cells. In addition, upregulation of miR-362-5p in SGC7901/DDP cells decreased the protein expression level of SUZ12, whereas downregulation of miR-362-5p increased the SUZ12 expression level. The results of the present study suggested that dysregulated miR-362-5p may target SUZ12 to promote the development of cisplatin resistance and attenuate cisplatin-induced apoptosis. Therefore, miR-362-5p upregulation combined with cisplatin treatment may serve as a promising therapeutic strategy for patients with cisplatin-resistant GC.