Department of Urology, Huashan Hospital, Fudan University, Shanghai 200040, China.
Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai 200040, China.
Aging (Albany NY). 2020 Apr 19;12(8):6865-6879. doi: 10.18632/aging.103047.
Circular RNAs (circRNAs) play an important role in bladder cancer (BC). Though circRNA involvement in BC has been reported, the underlying regulatory mechanisms are unknown. In this study, we performed EdU, CCK8, colony formation and Transwell assays to establish the role of circRGNEF in BC cell migration, proliferation, and invasion. We used bioinformatics and luciferase reporter experiments to investigate the regulatory mechanism. Nude mice xenografts and live imaging were used to explore the role of circRGNEF in tumor metastasis and growth. Expression profile analysis of human circRNAs in BC revealed that circRGNEF was upregulated significantly. High circRGNEF expression was correlated with aggressive BC phenotypes. The downregulation of circRGNEF suppressed BC cell metastasis and proliferation by targeting the miR-548/KIF2C axis and ; these results were verified with luciferase reporter assays. Our results show that miR-548 downregulation or KIF2C overexpression restored BC cell proliferation, migration, and invasion following silencing of circRGNEF. KIF2C overexpression reversed miR-548-induced cell invasion and migration as well as growth inhibition . In summary, the data illustrate that circRGNEF suppresses BC progression by functioning as a miR-548 sponge to enhance KIF2C expression. Therefore, circRGNEF might be a candidate BC treatment target.
环状 RNA(circRNAs)在膀胱癌(BC)中发挥重要作用。虽然已经报道了 circRNA 参与 BC,但潜在的调节机制尚不清楚。在这项研究中,我们进行了 EdU、CCK8、集落形成和 Transwell 测定,以确定 circRGNEF 在 BC 细胞迁移、增殖和侵袭中的作用。我们使用生物信息学和荧光素酶报告实验来研究调节机制。裸鼠异种移植和活体成像用于探索 circRGNEF 在肿瘤转移和生长中的作用。BC 中人类 circRNAs 的表达谱分析显示 circRGNEF 显著上调。高 circRGNEF 表达与侵袭性 BC 表型相关。circRGNEF 的下调通过靶向 miR-548/KIF2C 轴抑制 BC 细胞转移和增殖;这些结果通过荧光素酶报告实验得到验证。我们的结果表明,miR-548 下调或 KIF2C 过表达可恢复沉默 circRGNEF 后 BC 细胞的增殖、迁移和侵袭。KIF2C 过表达逆转了 miR-548 诱导的细胞侵袭和迁移以及生长抑制。总之,数据表明 circRGNEF 通过作为 miR-548 的海绵来增强 KIF2C 表达来抑制 BC 进展。因此,circRGNEF 可能是 BC 治疗的候选靶点。