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MiR-599 targeting TOP2A inhibits the malignancy of bladder cancer cells
1Department of Urology, Wuhan Sixth Hospital Affiliated to Jianghan University, Wuhan, 430015, Hubei, PR China.
Background:
Recent research suggests that many miRNAs influence the development of bladder cancer (BC). However, the function of the miR-599/TOP2A axis in BC cells is still unclear. Our aim was to verify the effect of the miR-599/TOP2A axis on BC progression.
Methods:
The expression of TOP2A and miR-599 in BC tissues and cells was detected using RT-qPCR. Luciferase assays, RIP assays, and RNA pull-down assays were performed to determine the interaction between miR-599 and TOP2A. CCK-8, flow cytometry-based apoptosis, wound healing, and Transwell assays were utilized to determine the proliferation, migration, invasion and apoptosis of BC cells.
Results:
MiR-599 was significantly downregulated in the BC, and miR-599 overexpression impeded the malignancy of BC cells by regulating proliferation, migration, invasion and apoptosis. TOP2A proved to a downstream target of miR-599 could enhance the tumorigenesis phenotype of BC cells. The experimental results also indicated that miR-599 reversed the oncogenic effects induced by TOP2A.
Conclusion:
Our study revealed that miR-599 represses BC tumorigenesis by inhibiting TOP2A.
Insights
MicroRNA-599 (miR-599) is downregulated in bladder cancer (BC) and inhibits tumor progression. Overexpression of miR-599 suppresses BC cell proliferation, migration, and invasion by targeting TOP2A.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNAs (miRNAs) play a role in bladder cancer (BC) development.
- The specific function of the miR-599/TOP2A pathway in BC remains largely unknown.
Purpose of the Study:
- To investigate the role of the miR-599/TOP2A axis in bladder cancer progression.
- To determine the functional impact of miR-599 on BC cell behavior.
Main Methods:
- Quantitative reverse transcription PCR (RT-qPCR) to measure TOP2A and miR-599 expression.
- Luciferase, RNA immunoprecipitation (RIP), and RNA pull-down assays to confirm miR-599 and TOP2A interaction.
- Cell proliferation (CCK-8), apoptosis (flow cytometry), migration (wound healing), and invasion (Transwell) assays to assess BC cell behavior.
Main Results:
- miR-599 expression was significantly reduced in bladder cancer tissues and cells.
- Overexpression of miR-599 inhibited BC cell proliferation, migration, and invasion, while promoting apoptosis.
- TOP2A was identified as a direct downstream target of miR-599.
- miR-599 overexpression reversed the oncogenic effects of TOP2A in BC cells.
Conclusions:
- miR-599 functions as a tumor suppressor in bladder cancer.
- The miR-599/TOP2A axis is a critical regulator of BC tumorigenesis.
- Inhibiting TOP2A through miR-599 represents a potential therapeutic strategy for bladder cancer.
