Abstract
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.