Circular RNA Ubiquitin-associated Protein 2 Silencing Suppresses Bladder Cancer Progression by Downregulating DNA Topoisomerase 2-alpha Through Sponging miR-496

环状 RNA 泛素相关蛋白 2 沉默通过吸收 miR-496 下调 DNA 拓扑异构酶 2-alpha 来抑制膀胱癌进展

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作者:Yang Fu, Kun Liu, Lun Zhao, Xi Jiang, Tianwei Wang

Background

Circular RNAs (circRNAs) have been uncovered to be implicated in the malignant development of bladder cancer (BC).

Conclusions

Silencing of circUBAP2 could suppress BC growth, invasion, migration, and aerobic glycolysis by the miR-496/TOP2A axis, suggesting a promising target for the molecular targeted therapies of BC. Patient summary: Circular RNA ubiquitin-associated protein 2 (circUBAP2) was found to be associated with poor prognosis in bladder cancer (BC). Knockdown of circUBAP2 might suppress BC growth, invasion, migration, and aerobic glycolysis, indicating that it may be a new target for the development of molecular targeted therapy for BC.

Objective

Herein, this work aimed to investigate the role and mechanism of circRNA ubiquitin-associated protein 2 (circUBAP2) in BC progression. Design setting and participants: Quantitative real-time polymerase chain reaction and Western blotting were used for the detection of genes and proteins. Outcome measurements and statistical analysis: In vitro functional experiments were conducted using colony formation, 5-ethynyl-2'-deoxyuridine (EdU), Transwell, wound healing, and flow cytometry assays, respectively. A glycolysis analysis was conducted by assessing glucose uptake and lactate production. A murine xenograft model was established to perform in vivo experiments. The binding interaction between miR-496 and circUBAP2 or DNA topoisomerase 2-alpha (TOP2A) was verified using a dual-luciferase reporter assay.

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