MicroRNA-524-5p increases cisplatin-sensitivity of gastric cancer cells by targeting SOX9 gene / 肿瘤

ABSTRACT

Objective: To investigate the mechanism of microRNA (miR)-524-5p mediating the effect of cisplatin in the treatment of gastric cancer. Methods: The level of miR-524-5p in gastric cancer tissues, the matched non-tumor tissues, cisplatin-resistant and parental gastric cancer cell lines was measured by real-time fluorescent quantitative PCR. The viability of cisplatin-resistant gastric cancer SGC-7901 and MKN-45 cells transfected with miR-524-5p mimics or the control RNA was detected by CCK-8 method. The expression of SRY-related high mobility group-box gene 9 (SOX9), a targeting protein of miR-524-5p, was identified by luciferase reporter assay and Western blotting. The “rescue” assay was used to explore the effect of SOX9 overexpression on the cisplatin-resistance of gastric cancer cells induced by miR-524-5p. Results: Compared with the normal gastric epithelial GES1 cells, the level of miR-524-5p in gastric cancer SGC-7901 and MKN-45 cells was significantly down-regulated (both P < 0.05); while the level of miR-524-5p in gastric cancer tissues was significantly lower than that in the adjacent non-tumor tissues (P < 0.05). After the treatment of cisplatin, the expression level of miR-524-5p in cisplatin-resistant gastric cancer SGC-7901 and MKN-45 cells was decreased as compared with the sensitive parental cells (both P< 0.05). After the transfection of miR-524-5p mimics, the sensitivity of cisplatin-resistant gastric cancer SGC-7901 and MKN-45 cells was significantly enhanced (both P< 0.05). Subsequently, SOX9 was identified as a functional target gene of miR-524-5p. Overexpression of SOX9 could counteract the chemosensitizing effect of miR-524-5p, in other words, the cisplatin-sensitivity of SGC-7901 and MKN-45 cells transfected with SOX9 overexpression plasmids and miR-524-5p mimics was significantly lower than that in single miR-524-5p mimics transfection group (both P< 0.05). Conclusion: The expression of miR-524-5p influences the sensitivity of human gastric cancer cells to cisplatin, suggesting that miR-524-5p has the potential to be a novel target for the treatment of chemoresistant gastric cancer patients.