Department of Obstetrics and Gynecology, Third Hospital, Peking University, Beijing 100191, China; Department of Obstetrics and Gynecology, He Nan Provincial People's Hospital, Zhengzhou 450000, China.
Department of Obstetrics and Gynecology, Third Hospital, Peking University, Beijing 100191, China.
Gene. 2019 Feb 20;686:63-67. doi: 10.1016/j.gene.2018.11.011. Epub 2018 Nov 5.
Drug-resistance of platinum remains a big challenge for effective treatment of patients with ovarian cancer. MicroRNAs (miRNAs) act as post-transcriptional regulators of gene expression and are associated with multi-drug resistance. Our study aims on identifying role of miRNAs in drug-resistance of platinum in ovarian cancer. In present study, we compared the expression profiles of miRNAs between three pairs of platinum-resistant and platinum-sensitive ovarian tissues and found that miR-509-3p was significantly down-regulated in cisplatin-resistant ovarian cancer tissues. The different expression of miR-509-3p was further determined by RT-qPCR analyses of tissue samples from groups of 20 patients with cisplatin-sensitive ovarian cancer and 7 patients with cisplatin-resistant ovarian cancer. Functional studies demonstrated that miR-509-3p inhibitor decreased cell response to cisplatin (CDDP) and promoted cell survival in SKOV3 ovarian cancer cells. Furthermore, we found gene expression level of Golgi phosphoprotein-3 (GOLPH3) and wntless Wnt ligand secretion mediator (WLS) were regulated by miR-509-3p. The direct bindings of miR-509-3p to GOLPH3 and WLS genes were confirmed by dual-luciferase reporter assay. And the negative correlation between their expression levels in SKOV3 cells was further verified with RT-qPCR. Altogether, our data provide preliminary evidence, supporting that targeting miR-509-3p might be a potential therapeutic strategy for patients with platinum-resistant ovarian cancer.
铂类耐药仍然是有效治疗卵巢癌患者的一大挑战。microRNAs（miRNAs）作为基因表达的转录后调节剂，与多药耐药有关。我们的研究旨在确定 miRNAs 在卵巢癌铂类耐药中的作用。在本研究中，我们比较了三对铂类耐药和铂类敏感卵巢组织中的 miRNAs 表达谱，发现 miR-509-3p 在顺铂耐药卵巢癌组织中明显下调。通过对 20 例顺铂敏感卵巢癌患者和 7 例顺铂耐药卵巢癌患者的组织样本进行 RT-qPCR 分析，进一步确定了 miR-509-3p 的不同表达。功能研究表明，miR-509-3p 抑制剂降低了 SKOV3 卵巢癌细胞对顺铂（CDDP）的细胞反应并促进了细胞存活。此外，我们发现高尔基磷酸蛋白-3（GOLPH3）和 Wnt 配体分泌介体（WLS）的基因表达水平受 miR-509-3p 调节。通过双荧光素酶报告基因实验证实了 miR-509-3p 对 GOLPH3 和 WLS 基因的直接结合。并通过 RT-qPCR 进一步验证了它们在 SKOV3 细胞中的表达水平呈负相关。总之，我们的数据提供了初步证据，表明靶向 miR-509-3p 可能是治疗铂类耐药卵巢癌患者的潜在治疗策略。
