文章：

MiR-216b通过靶向PARP1增加卵巢癌细胞对顺铂的敏感性

MiR-216b increases cisplatin sensitivity in ovarian cancer cells by targeting PARP1 

原文发布日期：2017-03-10 

英文摘要：

Cisplatin resistance hinders the efficacy of chemotherapy in ovarian cancer. MicroRNAs (miRs) have been implicated in drug resistance in anti-cancer chemotherapy. We compared the expression profiles of miRs between cisplatin-resistant and cisplatin-sensitive ovarian cancer cells, and found that miR-216b was significantly downregulated in cisplatin-resistant ovarian cancer cells. To investigate its molecular mechanism, we performed cell viability and apoptosis assays in cisplatin-resistant ovarian cells, and found that miR-216b reduced cell viability and promoted apoptosis. Although 4 potential targets were obtained through bioinformatics, only the mRNA level of poly(ADP-ribose) polymerase (PARP)-1 was significantly regulated by miR-216b. Disruption of the complementary binding sequence of miR-216b on the 3′-untranslated region (3′-UTR) of the PARP1 led to the loss of miR-216b targeting. Spearman’s correlation coefficient of the levels of miR-216b and PARP1 mRNA from 51 human ovarian cancer specimens also showed a significantly negative correlation between them. Importantly, the improved cisplatin sensitivity induced by miR-216b was markedly reversed by PARP1 overexpression. Tumor formation assay in nude mice further provided an evidence on the suppressive role of miR-216b in tumor growth. Taken together, this study demonstrated that a new miRNA, miR-216b, was involved in cisplatin resistance in ovarian cancer, which could be regarded as a potential sensitizer in cisplatin chemotherapy. 

摘要翻译： 

顺铂耐药性阻碍了卵巢癌化疗的疗效。MicroRNAs（miRs）已被证实与抗癌化疗中的耐药现象相关。通过比较顺铂耐药与顺铂敏感卵巢癌细胞的miR表达谱，我们发现miR-216b在顺铂耐药细胞中显著下调。为探究其分子机制，我们在顺铂耐药卵巢癌细胞中进行细胞活力和凋亡实验，发现miR-216b可降低细胞活力并促进凋亡。虽通过生物信息学分析获得4个潜在靶标，但仅有聚腺苷二磷酸核糖聚合酶（PARP）-1的mRNA水平受到miR-216b的显著调控。破坏PARP1基因3'-非翻译区（3'-UTR）上miR-216b的互补结合序列后，该靶向作用随之消失。对51例人类卵巢癌标本的检测数据显示，miR-216b与PARP1 mRNA水平呈显著负相关（斯皮尔曼相关系数）。重要的是，miR-216b所增强的顺铂敏感性可被PARP1过表达显著逆转。裸鼠体内成瘤实验进一步证实了miR-216b抑制肿瘤生长的作用。本研究首次证实新型miRNA——miR-216b参与卵巢癌顺铂耐药过程，该分子可作为顺铂化疗的潜在增敏剂。

原文链接：

MiR-216b increases cisplatin sensitivity in ovarian cancer cells by targeting PARP1