Niu Yi-Chao, Tong Jing, Shi Xiao-Fei, Zhang Ting
Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200135, P.R. China.
Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai 200135, P.R. China.
Exp Ther Med. 2020 Aug;20(2):1467-1479. doi: 10.3892/etm.2020.8878. Epub 2020 Jun 11.
Dysregulation of microRNAs serves a crucial role in the chemosensitivity to cisplatin (DDP) in ovarian cancer (OVC). The abnormal expression of microRNA (miR)-654-3p has been reported in several types of human cancer. However, the association between miR-654-3p and cisplatin resistance in human OVC remains unclear. The present study aimed to investigate the role and mechanism of miR-654-3p in DDP resistance in OVC. The results demonstrated that miR-654-3p was significantly downregulated in ovarian cancer tissues and cells, as well as DDP-resistant IGROV-1/DDP cells, compared with adjacent non-tumoral tissue and IOSE386 cells. Overexpression of miR-654-3p significantly suppressed the proliferation and migration of ovarian cancer cells and increased the sensitivity of IGROV-1/DDP cells to DDP. Luciferase reporter assay demonstrated that quinolinate phosphoribosyl transferase (QPRT) was a target of miR-654-3p; overexpression of miR-654-3p inhibited QPRT expression by binding to the 3'-untranslated region of QPRT. In addition, inhibition of miR-654-3p reversed the suppressive effects of QPRT-targeting short interfering RNA on the proliferation and chemoresistance of ovarian cancer cells. Therefore, the results of the present study revealed a previously unrecognized regulatory mechanism that miR-654-3p enhances DDP sensitivity of OVC cells by downregulating QPRT expression; in addition, the present study highlighted the therapeutic implications of miR-654-3p upregulation in OVC.
微小RNA的失调在卵巢癌（OVC）对顺铂（DDP）的化疗敏感性中起关键作用。据报道，微小RNA（miR）-654-3p在几种类型的人类癌症中存在异常表达。然而，miR-654-3p与人类OVC顺铂耐药性之间的关联仍不清楚。本研究旨在探讨miR-654-3p在OVC顺铂耐药中的作用及机制。结果表明，与相邻非肿瘤组织和IOSE386细胞相比，miR-654-3p在卵巢癌组织和细胞以及顺铂耐药的IGROV-1/DDP细胞中显著下调。miR-654-3p的过表达显著抑制了卵巢癌细胞的增殖和迁移，并增加了IGROV-1/DDP细胞对DDP的敏感性。荧光素酶报告基因检测表明喹啉酸磷酸核糖基转移酶（QPRT）是miR-654-3p的靶标；miR-654-3p的过表达通过与QPRT的3'非翻译区结合抑制QPRT表达。此外，抑制miR-654-3p可逆转靶向QPRT的小干扰RNA对卵巢癌细胞增殖和化疗耐药性的抑制作用。因此，本研究结果揭示了一种先前未被认识的调控机制，即miR-654-3p通过下调QPRT表达增强OVC细胞对DDP的敏感性；此外，本研究突出了上调miR-654-3p在OVC中的治疗意义。
