BACKGROUND Cisplatin resistance (DDP-resistance) remains one of the major causes of poor prognosis in females with ovarian cancer. Long non-coding RNAs (lncRNAs) have been shown to participate in the regulation of cellular processes, including chemoresistance. The aim of this study was to explore the role of HOX transcript antisense RNA (HOTAIR) in DDP-resistant ovarian cancer cells. METHODS DDP-resistant ovarian cancer cell lines (SKOV3/DDP and A2780/DDP) were established. Real-time PCR, western blot, dual-luciferase reporter assay, and flow cytometry were then used to evaluate the effect of HOTAIR/miR-138-5p axis on chemoresistance of DDP-resistant ovarian cancer cells to DDP. RESULTS We found that HOTAIR was upregulated in DDP-resistant cells, while miR-138-5p was downregulated. Knockdown of HOTAIR increased the expression of miR-138-5p in DDP-resistant cells and miR-138-5p is directly bound to HOTAIR. Upregulation of miR-138-5p induced by HOTAIR siRNA or by its mimics enhanced the chemosensitivity of DDP-resistant cells and decreased the expression of EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit) and SIRT1 (sirtuin 1). Furthermore, the HOTAIR silencing-induced chemosensitivity of DDP-resistant cells was weakened by miR-138-5p inhibitor. CONCLUSIONS These data demonstrate that HOTAIR acts as a sponge of miR-138-5p to prevent its binding to EZH2 and SIRT1, thereby promoting DDP-resistance of ovarian cancer cells. Our work will shed light on the development of therapeutic strategies for ovarian cancer treatment.

中文翻译：

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抑制长的非编码RNA HOTAIR通过抑制miR-138-5p调节的EZH2和SIRT1逆转卵巢癌细胞的顺铂耐药性。

背景技术顺铂耐药性（DDP耐药性）仍然是卵巢癌女性预后不良的主要原因之一。长的非编码RNA（lncRNA）已显示参与细胞过程的调控，包括化学抗性。这项研究的目的是探索HOX转录反义RNA（HOTAIR）在抗DDP的卵巢癌细胞中的作用。方法建立抗DDP的卵巢癌细胞株（SKOV3 / DDP和A2780 / DDP）。然后使用实时荧光定量PCR，蛋白质印迹，双荧光素酶报告基因测定和流式细胞术评估HOTAIR / miR-138-5p轴对DDP耐药卵巢癌细胞对DDP的化学耐药性的影响。结果我们发现HOTAIR在DDP耐药细胞中被上调，而miR-138-5p被下调。击倒HOTAIR增加了在DDP耐药细胞中miR-138-5p的表达，而miR-138-5p直接与HOTAIR结合。HOTAIR siRNA或其模拟物诱导的miR-138-5p上调增强了DDP耐药细胞的化学敏感性，并降低了EZH2（zeste 2聚梳抑制复合物2亚基的增强子）和SIRT1（sirtuin 1）的表达。此外，miR-138-5p抑制剂减弱了HOTAIR沉默诱导的DDP耐药细胞的化学敏感性。结论这些数据表明，HOTAIR充当miR-138-5p的海绵，可防止其与EZH2和SIRT1结合，从而促进卵巢癌细胞的DDP抗性。我们的工作将阐明卵巢癌治疗策略的发展。HOTAIR siRNA或其模拟物诱导的miR-138-5p上调增强了DDP耐药细胞的化学敏感性，并降低了EZH2（zeste 2聚梳抑制复合物2亚基的增强子）和SIRT1（sirtuin 1）的表达。此外，miR-138-5p抑制剂减弱了HOTAIR沉默诱导的DDP耐药细胞的化学敏感性。结论这些数据表明，HOTAIR充当miR-138-5p的海绵，可防止其与EZH2和SIRT1结合，从而促进卵巢癌细胞的DDP抗性。我们的工作将阐明卵巢癌治疗策略的发展。HOTAIR siRNA或其模拟物诱导的miR-138-5p上调增强了DDP耐药细胞的化学敏感性，并降低了EZH2（zeste 2聚梳抑制复合物2亚基的增强子）和SIRT1（sirtuin 1）的表达。此外，miR-138-5p抑制剂减弱了HOTAIR沉默诱导的DDP耐药细胞的化学敏感性。结论这些数据表明，HOTAIR充当miR-138-5p的海绵，可防止其与EZH2和SIRT1结合，从而促进卵巢癌细胞的DDP抗性。我们的工作将阐明卵巢癌治疗策略的发展。miR-138-5p抑制剂减弱了HOTAIR沉默诱导的DDP耐药细胞的化学敏感性。结论这些数据表明，HOTAIR充当miR-138-5p的海绵，可防止其与EZH2和SIRT1结合，从而促进卵巢癌细胞的DDP抗性。我们的工作将阐明卵巢癌治疗策略的发展。miR-138-5p抑制剂减弱了HOTAIR沉默诱导的DDP耐药细胞的化学敏感性。结论这些数据表明，HOTAIR充当miR-138-5p的海绵，可防止其与EZH2和SIRT1结合，从而促进卵巢癌细胞的DDP抗性。我们的工作将阐明卵巢癌治疗策略的发展。