Department of Thoracic Surgery, Shengjing Hospital, China Medical University, Shenyang, Liaoning, China.
Department of Thoracic Surgery, Shengjing Hospital, China Medical University, Shenyang, Liaoning, China.
Biomed Pharmacother. 2020 Apr;124:109828. doi: 10.1016/j.biopha.2020.109828. Epub 2020 Jan 24.
Recently, increasing studies have confirmed some circRNAs were involved in the genesis of chemotherapy resistance in almost all kinds of malignant tumors, including lung adenocarcinoma (LAD). Nevertheless, the function and mechanism of circPVT1 in regulating chemotherapy resistance of LAD has not been elucidated so far. The current study found circPVT1 was highly expressed in LAD, which expression was positively related to N stage and chemotherapy insensitivity (cisplatin and pemetrexed) of LAD patients, and it was an independent prognostic biomarker for LAD patients. The circPVT1 expression was up-regulated in LAD tissues and cell line (A549/DR) resistant to cisplatin and pemetrexed. CircPVT1 knockdown sensitized A549/DR cells to cisplatin and pemetrexed. RNA pull-down assay et al. confirmed circPVT1 acted as a ceRNA for miR-145-5p in A549/DR cells. In addition, miR-145-5p was lowly expressed in cisplatin and pemetrexed resistant LAD tissues and cell line, and its over-expression also sensitized A549/DR cells to cisplatin and pemetrexed. The luciferase reporter assay et al. proved ABCC1 was a target gene of miR-145-5p in A549/DR cells. Moreover, miR-145-5p enhancement partly restored the effecting of circPVT1 knockdown on chemotherapy resistance in A549/DR cells, miR-145-5p/ABCC1 pathway mediated chemotherapy resistance induced by circPVT1 knockdown in LAD cells. In conclusion, the high-expression of circPVT1 is related with the cisplatin and pemetrexed insensitivity of LAD patients, circPVT1 contributes to cisplatin and pemetrexed chemotherapy resistance through miR-145-5p/ABCC1 axis.
最近，越来越多的研究证实，circRNAs 参与了几乎所有恶性肿瘤包括肺腺癌（LAD）的化疗耐药的发生。然而，circPVT1 调节 LAD 化疗耐药的功能和机制尚未阐明。本研究发现 circPVT1 在 LAD 中高表达，其表达与 LAD 患者的 N 分期和化疗不敏感（顺铂和培美曲塞）呈正相关，是 LAD 患者的独立预后生物标志物。circPVT1 在 LAD 组织和对顺铂和培美曲塞耐药的细胞系（A549/DR）中上调。circPVT1 敲低可使 A549/DR 细胞对顺铂和培美曲塞敏感。RNA 下拉实验等证实 circPVT1 作为 A549/DR 细胞中 miR-145-5p 的 ceRNA 发挥作用。此外，miR-145-5p 在顺铂和培美曲塞耐药的 LAD 组织和细胞系中低表达，其过表达也使 A549/DR 细胞对顺铂和培美曲塞敏感。荧光素酶报告实验等证实 ABCC1 是 A549/DR 细胞中 miR-145-5p 的靶基因。此外，miR-145-5p 增强部分恢复了 circPVT1 敲低对 A549/DR 细胞化疗耐药的影响，miR-145-5p/ABCC1 通路介导 circPVT1 敲低在 LAD 细胞中引起的化疗耐药。总之，circPVT1 的高表达与 LAD 患者对顺铂和培美曲塞的不敏感有关，circPVT1 通过 miR-145-5p/ABCC1 轴促进顺铂和培美曲塞化疗耐药。
