MicroRNA-27a regulates the proliferation, chemosensitivity and invasion of human ovarian cancer cell lines by targeting Cullin 5 (Retracted Article)
MicroRNA-27a regulates the proliferation, chemosensitivity and invasion of human ovarian cancer cell lines by targeting Cullin 5 (Retracted Article)
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DOI：
10.1016/j.abb.2019.04.009
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发表时间：
2019-06-15
影响因子：
3.9
通讯作者：
Yang, Shuli
中科院分区：
文献类型：
--
作者：
Si, Lihui;Jia, Yan;Yang, Shuli
报告表明，microRNA在包括癌症在内的几种疾病的发展中具有影响。因此，认为miR可以充当癌症治疗的治疗靶标。卵巢癌的治疗主要受到缺乏生物标志物和有效药物靶点的阻碍。在此背景下，本研究旨在揭示miR-27a在卵巢癌中的治疗意义。结果显示，miR-27 a在卵巢癌组织和细胞系中的表达明显升高。抑制miR-27 a表达可导致SK-OV-3和OVACAR-3细胞增殖率和集落形成能力下降，并发生G（2）/M阻滞。miR-27 a抑制触发SK-OV-3和OVACAR-3细胞的G（2）/M阻滞，伴随着细胞周期蛋白A和B1表达水平的耗竭。TargetScan分析和双报告基因分析显示miR-27 a通过调节CUL5表达发挥其作用。CUL5在卵巢癌组织和细胞系中被抑制，并且miR-27 a表达的抑制引起CUL5表达的上调。过表达CUL5可通过诱导G（2）/M期阻滞抑制SK-OV-3和OVACAR-3细胞增殖，与miR-27 a抑制作用相似。有趣的是，CUL5过表达逆转了miR-27 a抑制对SK-0V-3细胞活力的影响。抑制miR-27 a可以增强SK-OV-3细胞对顺铂和多西他赛抗癌药物的化疗敏感性，并降低其迁移和侵袭。这项研究的结果表明，miR-27 a抑制抑制卵巢癌的生长，化疗敏感性和侵袭性，并可能证明在卵巢癌的管理有益。
Reports suggest that microRNAs have implications in the development of several diseases including cancer. It is therefore believed that miRs may act as therapeutic targets for cancer treatment. The treatment of ovarian cancer is mainly obstructed by lack of biomarkers and efficient drug targets. Against this backdrop, this study was undertaken to unveil the therapeutic implications of miR-27a in ovarian cancer. The results showed that the expression of miR-27a was significantly elevated in ovarian cancer tissues and cell lines. Inhibition of miR-27a expression resulted in the decrease of proliferation rate and colony formation potential of the SK-OV-3 and OVACAR-3 cells via G(2)/M arrest. The miR-27a inhibition triggered G(2)/M arrest of SK-OV-3 and OVACAR-3 cells was accompanied with depletion of cyclin A and B1 expression levels. TargetScan analysis together with dual reporter assay revealed that miR-27a exerts its effects via modulation of CUL5 expression. The CUL5 was shown to be suppressed in the ovarian cancer tissues and cell lines and suppression of miR-27a expression caused upregulation of CUL5 expression. Overexpression of CUL5 caused inhibition of SK-OV-3 and OVACAR-3 cell proliferation via induction of G(2)/M arrest, similar to that of miR-27a inhibition. Interestingly, CUL5 over expression reversed the effects of miR-27a inhibition on the viability of SK-OV-3 cells. Finally, the suppression of miR-27a could enhance the chemosensitivity of the SK-OV-3 cells to cisplatin and docetaxel anticancer drugs and also decreased their migration and invasion. The findings of this study revealed that miR-27a suppression inhibits the growth, chemosensitivity and invasion of ovarian cancer and may prove beneficial in the ovarian cancer management.