Department of Obstetrics and Gynecology, The Second Hospital of Taizhou, Taizhou City, Jiangsu Province 225500, China.
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China.
Biosci Rep. 2020 Apr 30;40(4). doi: 10.1042/BSR20192457.
Ovarian cancer (OC) is a malignant tumor with high mortality in women. Although cancer patients initially respond to paclitaxel chemotherapy following surgery, most patients will relapse after 12-24 months and gradually die from chemotherapy resistance. In OC, cancer cells become resistant to paclitaxel chemotherapy under hypoxic environment. The miR-27a has been identified as an oncogenic molecular in ovarian cancer, prostate cancer, liver cancer etc. In addition, the miR-27a is involved in hypoxia-induced chemoresistance in various cancers. However, the role of miR-27a in hypoxia-induced OC resistance remains unclear. The aim of the present study was to investigate the regulatory mechanism of miR-27a in hypoxia-induced OC resistance. The expression of HIF-1α induced Hypoxia overtly up-regulated. At the same time, hypoxia increased viability of Skov3 cells and decreased cell apoptosis when treated with paclitaxel. The expression of the miR-27a was obviously up-regulated under hypoxia and involved in hypoxia-induced paclitaxel resistance. Follow-up experiments portray that miR-27a improved paclitaxel resistance by restraining the expression of APAF1 in OC. Finally, we further elucidated the important regulatory role of the miR-27a-APAF1 axis in OC through in vivo experiments. According to our knowledge, we first reported the regulation of miR-27a in hypoxia-induced chemoresistance in OC, providing a possible target for chemoresistance treatment of OC.
卵巢癌（OC）是一种女性死亡率较高的恶性肿瘤。尽管癌症患者在手术后最初对紫杉醇化疗有反应，但大多数患者在 12-24 个月后会复发，并逐渐因化疗耐药而死亡。在 OC 中，癌细胞在缺氧环境下对紫杉醇化疗产生耐药性。miR-27a 已被确定为卵巢癌、前列腺癌、肝癌等的致癌分子。此外，miR-27a 参与各种癌症中缺氧诱导的化疗耐药性。然而，miR-27a 在缺氧诱导的 OC 耐药性中的作用尚不清楚。本研究旨在探讨 miR-27a 在缺氧诱导的 OC 耐药性中的调节机制。HIF-1α 的表达诱导缺氧明显上调。同时，缺氧增加了紫杉醇处理的 Skov3 细胞的活力并减少了细胞凋亡。miR-27a 的表达在缺氧下明显上调，并参与了缺氧诱导的紫杉醇耐药性。后续实验表明，miR-27a 通过抑制 APAF1 在 OC 中的表达来提高紫杉醇耐药性。最后，我们通过体内实验进一步阐明了 miR-27a-APAF1 轴在 OC 中的重要调节作用。据我们所知，我们首次报道了 miR-27a 在 OC 中缺氧诱导的化疗耐药性中的调节作用，为 OC 的化疗耐药性治疗提供了一个可能的靶点。
