miR-483-5p在上皮性卵巢癌中的表达及其对顺铂敏感性的影响

摘要

Background and purpose:Although cisplatin-based chemotherapies are used as the first-line treatment for ovarian cancers, the majority of patients eventually progress with platinum-resistant disease. miR-483-5p is overexpressed in lung cancer. However, the research on miR-483-5p in epithelial ovarian cancer (EOC) is still unclear. This study aimed to investigate the expression of miR-483-5p in EOC and its effects on cisplatin resistance in EOC cells.Methods:This study analyzed the expression of the miR-483-5p by real-time lfuorescent quantitative polymerase chain reaction (RTFQ-PCR) in EOC tissues, normal ovarian tissues, and EOC cells. The role of miR-483-5p in EOC was evaluatedin vitro by lentivirus-mediated knockdown of miR-483-5p or overexpression of miR-483-5p in EOC cell lines. Drug sensitivity assay was carried out by CCK-8 kit.Results:miR-483-5p was upregulated in EOC tissues as compared with normal tissues (P<0.01). Furthermore, miR-483-5p expression in advanced stage (Ⅲ–Ⅳ) EOC was significantly higher than that in early stage (Ⅰ–Ⅱ) EOC (P<0.05). Interestingly, miR-483-5p expression was higher in cisplatin-resistant A2780/CP cells than other cells. Increased miR-483-5p expression caused EOC cell resistance to cisplatin and downregulated the expression of p21 and Bcl-2, whereas reduced miR-483-5p expression induced its sensitivity and upregulated the expression of p21 and Bcl-2.Conclusion:The results suggest that miR-483-5p is highly expressed in EOC and contributes to cisplatin resistance. Thus, miR-483-5p is a potential therapeutic target for ovarian cancer.%背景与目的：顺铂是目前临床上治疗上皮性卵巢癌的一线化疗药物之一，但许多患者对铂类药物耐药。miR-483-5p在肺癌中过表达，然而目前尚未见miR-483-5p在上皮性卵巢癌中的研究。该研究检测miR-483-5p在上皮性卵巢癌组织和上皮性卵巢癌细胞系中的表达并探讨其对上皮性卵巢癌细胞对顺铂敏感性的影响。方法：采用实时荧光定量聚合酶链反应(real-time fluorescent quantitative polymerase chain reaction，RTFQ-PCR)检测43例上皮性卵巢癌患者的肿瘤组织、8例正常卵巢组织和5种上皮性卵巢癌细胞系中miR-483-5p的表达情况；通过慢病毒上调或敲低卵巢癌细胞miR-483-5p表达，应用CCK-8实验检测miR-483-5p对上皮性卵巢癌细胞系顺铂敏感性的影响。结果：上皮性卵巢癌组织中miR-483-5p表达明显高于正常卵巢组织(P<0.01)。此外，miR-483-5p在晚期上皮性卵巢癌组织中的表达水平显著高于早期肿瘤组织(P<0.05)。5种上皮性卵巢癌细胞系中SKOV3细胞表达miR-483-5p的量最低；miR-483-5p在上皮性卵巢癌顺铂耐药A2780/CP细胞中表达量最高。上调SKOV3细胞中miR-483-5p的表达能够降低上皮性卵巢癌细胞对顺铂的敏感性，并下调p21及Bcl-2的表达；下调A2780/CP细胞miR-483-5p的表达能够增加细胞对顺铂的敏感性，并上调p21及Bcl-2的表达。结论：miR-483-5p在上皮性卵巢癌组织中高表达并对顺铂耐药，可以作为临床预测上皮性卵巢癌对顺铂敏感性的生物标志物之一。