Hypoxia-induced up-regulation of miR-27a promotes paclitaxel resistance in ovarian cancer
Hypoxia-induced up-regulation of miR-27a promotes paclitaxel resistance in ovarian cancer
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DOI：
10.1042/bsr20192457
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发表时间：
2020-03-31
影响因子：
4
通讯作者：
Chen, Youguo
中科院分区：
文献类型：
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作者：
Feng, Lanlan;Shen, Fangrong;Chen, Youguo
卵巢癌（Ovarian cancer，OC）是一种女性死亡率高的恶性肿瘤。虽然癌症患者在手术后对紫杉醇化疗最初有反应，但大多数患者会在12-24个月后复发，并逐渐死于化疗耐药性。在OC中，癌细胞在缺氧环境下对紫杉醇化疗产生耐药性。miR-27 a已被鉴定为卵巢癌、前列腺癌、肝癌等的致癌分子。此外，miR-27 a还参与了多种癌症中低氧诱导的化疗耐药性。然而，miR-27 a在缺氧诱导的OC抵抗中的作用仍不清楚。本研究旨在探讨miR-27 a在缺氧诱导OC抵抗中的调控机制。缺氧诱导的HIF-1 α表达明显上调。同时，缺氧增加了Skov 3细胞的活力，减少了紫杉醇处理后的细胞凋亡。低氧条件下，miR-27 a的表达明显上调，并参与低氧诱导的紫杉醇耐药。后续实验显示miR-27 a通过抑制OC中APAF 1的表达而改善了OC对紫杉醇的耐药性。最后，我们通过体内实验进一步阐明了miR-27 a-APAF 1轴在OC中的重要调控作用。据我们所知，我们首次报道了miR-27 a在缺氧诱导的OC耐药中的调控作用，为OC耐药治疗提供了一个可能的靶点。
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-1 alpha 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.