Zhao Henan, Yu Xiaotang, Ding Yanfang, Zhao Jinyao, Wang Guang, Wu Xian, Jiang Jiyong, Peng Chun, Guo Gordon Zhuo, Cui Shiying
Dalian Medical University, Dalian, China.
Obstetrics and Gynecology Hospital, Dalian, China.
Oncotarget. 2016 Aug 16;7(33):53254-53268. doi: 10.18632/oncotarget.10736.
In this study, we examined the role of the miRNA miR-770-5p in cisplatin chemotherapy resistance in ovarian cancer (OVC) patients. miR-770-5p expression was reduced in platinum-resistant patients. Using a 6.128-fold in expression as the cutoff value, miR-770-5p expression served as a prognostic biomarker and predicted the response to cisplatin treatment and survival among OVC patients. Overexpression of miR-770-5p in vitro reduced survival in chemoresistant cell lines after cisplatin treatment. ERCC2, a target gene of miR-770-5p that participates in the NER system, was negatively regulated by miR-770-5p. siRNA-mediated silencing of ERCC2 reversed the inhibition of apoptosis resulting from miR-770-5p downreglation in A2780S cells. A comet assay confirmed that this restoration of cisplatin chemosensitivity was due to the inhibition of DNA repair. These findings suggest that endogenous miR-770-5p may function as an anti-oncogene and promote chemosensitivity in OVC, at least in part by downregulating ERCC2. miR-770-5p may therefore be a useful biomarker for predicting chemosensitivity to cisplatin in OVC patients and improve the selection of effective, more personalized, treatment strategies.
在本研究中，我们检测了微小RNA miR-770-5p在卵巢癌（OVC）患者顺铂化疗耐药中的作用。铂类耐药患者中miR-770-5p表达降低。以6.128倍的表达量作为临界值，miR-770-5p表达可作为一种预后生物标志物，并预测OVC患者对顺铂治疗的反应及生存情况。体外过表达miR-770-5p可降低顺铂处理后化疗耐药细胞系的存活率。ERCC2是miR-770-5p的一个靶基因，参与核苷酸切除修复（NER）系统，受miR-770-5p负调控。小干扰RNA（siRNA）介导的ERCC2沉默可逆转A2780S细胞中因miR-770-5p下调导致的细胞凋亡抑制。彗星试验证实顺铂化疗敏感性的恢复是由于DNA修复受到抑制。这些发现表明，内源性miR-770-5p可能作为一种抑癌基因发挥作用，并至少部分通过下调ERCC2来促进OVC的化疗敏感性。因此，miR-770-5p可能是预测OVC患者对顺铂化疗敏感性的有用生物标志物，并有助于改进有效、更具个性化的治疗策略的选择。
