Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
Xiangya School of Medicine, Central South University, Changsha, Hunan 410011, China
Cell Cycle. 2018;17(4):448-458. doi: 10.1080/15384101.2017.1395533. Epub 2018 Feb 8.
Cisplatin (DDP) -based chemotherapy is a standard strategy for cervical cancer, while chemoresistance remains a huge challenge. Copper transporter protein 1 (CTR1), a copper influx transporter required for high affinity copper (probably reduced Cu I) transport into the cell, reportedly promotes a significant fraction of DDP internalization in tumor cells. In the present study, we evaluated the function of CTR1 in the cell proliferation of cervical cancer upon DDP treatment. MicroRNAs (miRNAs) have been regarded as essential regulators of cell proliferation, apoptosis, migration, as well as chemoresistance. By using online tools, we screened for candidate miRNAs potentially regulate CTR1, among which miR-130a has been proved to promote cervical cancer cell proliferation through targeting PTEN in our previous study. In the present study, we investigated the role of miR-130a in cervical cancer chemoresistance to DDP, and confirmed the binding of miR-130a to CTR1. SOX9 also reportedly act on cancer chemoresistance. In the present study, we revealed that SOX9 inversely regulated miR-130a through direct targeting the promoter of miR-130a. Consistent with previous studies, SOX9 could affect cervical cancer chemoresistance to DDP. Taken together, we demonstrated a SOX9/miR-130a/CTR1 axis which modulated the chemoresistance of cervical cancer cell to DDP, and provided promising targets for dealing with the chemoresistance of cervical cancer.
顺铂(DDP)为基础的化疗是宫颈癌的标准策略,而化疗耐药仍然是一个巨大的挑战。铜转运蛋白 1(CTR1),一种铜输入转运体,需要高亲和力的铜(可能是还原的 Cu I)进入细胞,据报道,它促进了肿瘤细胞中 DDP 内化的很大一部分。在本研究中,我们评估了 CTR1 在顺铂处理后宫颈癌细胞增殖中的功能。微小 RNA(miRNA)已被认为是细胞增殖、凋亡、迁移以及化疗耐药的重要调节因子。通过使用在线工具,我们筛选出潜在调节 CTR1 的候选 miRNA,其中 miR-130a 在我们之前的研究中已被证明通过靶向 PTEN 促进宫颈癌细胞增殖。在本研究中,我们研究了 miR-130a 在宫颈癌对 DDP 化疗耐药中的作用,并证实了 miR-130a 与 CTR1 的结合。SOX9 也被报道对癌症化疗耐药有影响。在本研究中,我们揭示了 SOX9 通过直接靶向 miR-130a 的启动子来反向调节 miR-130a。与之前的研究一致,SOX9 可以影响宫颈癌对 DDP 的化疗耐药性。综上所述,我们证实了 SOX9/miR-130a/CTR1 轴调节宫颈癌细胞对 DDP 的化疗耐药性,并为解决宫颈癌化疗耐药性提供了有前途的靶点。