Liu Weiwei, Yao Dongmei, Huang Bo
Department of Gynecology, Maternal and Child Health Hospital of Hubei Province, Wuhan, Hubei, 430070, China.
Department of Gynaecology and Obstetrics, Hubei General Hospital, No. 99 ZhangZhiDong Street, Wuchang District, Wuhan, Hubei, 430060, China.
Open Life Sci. 2021 Jan 21;16(1):1-13. doi: 10.1515/biol-2021-0002. eCollection 2021.
Cervical cancer (CC) is a huge threat to the health of women worldwide. Long non-coding RNA plasmacytoma variant translocation 1 gene (PVT1) was proved to be associated with the development of diverse human cancers, including CC. Nevertheless, the exact mechanism of PVT1 in CC progression remains unclear. Levels of PVT1, microRNA-503 (miR-503), and ADP ribosylation factor-like protein 2 (ARL2) were measured by quantitative reverse transcription-polymerase chain reaction or western blot assay. 3-(4,5)-Dimethylthiazole-2-y1)-2,5-biphenyl tetrazolium bromide (MTT) and flow cytometry were used to examine cell viability and apoptosis, respectively. For migration and invasion detection, transwell assay was performed. The interaction between miR-503 and PVT1 or ARL2 was shown by dual luciferase reporter assay. A nude mouse model was constructed to clarify the role of PVT1 . PVT1 and ARL2 expressions were increased, whereas miR-503 expression was decreased in CC tissues and cells. PVT1 was a sponge of miR-503, and miR-503 targeted ARL2. PVT1 knockdown suppressed proliferation, migration, and invasion of CC cells, which could be largely reverted by miR-503 inhibitor. In addition, upregulated ARL2 could attenuate si-PVT1-mediated anti-proliferation and anti-metastasis effects on CC cells. Silenced PVT1 also inhibited CC tumor growth . PVT1 knockdown exerted tumor suppressor role in CC progression via the miR-503/ARL2 axis, at least in part.
宫颈癌（CC）对全球女性的健康构成巨大威胁。长链非编码RNA浆细胞瘤变体易位1基因（PVT1）已被证明与包括CC在内的多种人类癌症的发生发展有关。然而，PVT1在CC进展中的确切机制仍不清楚。通过定量逆转录-聚合酶链反应或蛋白质免疫印迹法检测PVT1、微小RNA-503（miR-503）和ADP核糖基化因子样蛋白2（ARL2）的水平。分别采用3-(4,5)-二甲基噻唑-2-基)-2,5-联苯四氮唑溴盐（MTT）法和流式细胞术检测细胞活力和凋亡情况。采用Transwell实验检测细胞迁移和侵袭能力。通过双荧光素酶报告基因实验显示miR-503与PVT1或ARL2之间的相互作用。构建裸鼠模型以阐明PVT1的作用。CC组织和细胞中PVT1和ARL2表达上调，而miR-503表达下调。PVT1是miR-503的海绵，miR-503靶向ARL2。敲低PVT1可抑制CC细胞的增殖、迁移和侵袭，miR-503抑制剂可在很大程度上逆转这种抑制作用。此外，上调ARL2可减弱si-PVT1介导的对CC细胞的抗增殖和抗转移作用。沉默PVT1也可抑制CC肿瘤生长。敲低PVT1至少部分通过miR-503/ARL2轴在CC进展中发挥肿瘤抑制作用。
