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CircRNA-Cdr1as Exerts Anti-Oncogenic Functions in Bladder Cancer by Sponging MicroRNA-135a
Peng Li1,2, Xiao Yang1, Wenbo Yuan1
1Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Background/Aims:
CircRNAs regulate gene expression in different malignancies. However, the role of Cdr1as in the tumourigenesis of bladder cancer and its potential mechanisms remain unknown.
Methods:
qRT-PCR was used to detect Cdr1as and target miRNA expression in bladder cancer tissues and cell lines. Biological functional experiments were performed to detect the effects of Cdr1as on the biological behaviour of bladder cancer cells in vivo and in vitro. Bioinformatic analysis was utilised to predict potential miRNA target sites on Cdr1as. Ago2 RNA binding protein immunoprecipitation assay, RNA antisense purification assay, biotin pull down assay and RNA FISH were performed to detect the interaction between Cdr1as and target miRNAs. Western blot was used to determine the expression level of p21 in bladder cancer cells.
Results:
Cdr1as was significantly down-regulated in bladder cancer tissues compared with adjacent normal tissues. Overexpression of Cdr1as inhibited the proliferation, invasion and migration of bladder cancer cells in vitro and slowed down tumour growth in vivo. Cdr1as sponged multiple miRNAs in bladder cancer. Moreover, Cdr1as directly bound to miR-135a and inhibited its activity in bladder cancer.
Conclusion:
Cdr1as is down-regulated and sponges multiple miRNAs in bladder cancer. It exerts anti-oncogenic functions by sponging microRNA-135a.
Insights
Circular RNAs (CircRNAs) like Cdr1as are downregulated in bladder cancer, inhibiting tumor growth by sponging microRNA-135a. This finding reveals Cdr1as as a potential therapeutic target for bladder cancer treatment.
Area of Science:
- Molecular Biology
- Oncology
- Gene Regulation
Background:
- Circular RNAs (CircRNAs) are implicated in various cancers.
- The specific role and mechanism of Cdr1as in bladder cancer tumorigenesis were previously unknown.
Purpose of the Study:
- To investigate the role of Cdr1as in bladder cancer development.
- To elucidate the underlying molecular mechanisms of Cdr1as in bladder cancer.
Main Methods:
- Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) for expression analysis.
- In vitro and in vivo functional assays to assess Cdr1as effects on bladder cancer cell behavior.
- Bioinformatic analysis, Ago2 immunoprecipitation, RNA pull-down, and FISH to confirm Cdr1as-miRNA interactions.
Main Results:
- Cdr1as expression was significantly reduced in bladder cancer tissues.
- Overexpressing Cdr1as suppressed bladder cancer cell proliferation, invasion, and migration.
- Cdr1as directly interacted with and inhibited miR-135a activity, acting as a miRNA sponge.
Conclusions:
- Cdr1as functions as an anti-oncogene in bladder cancer by downregulating miR-135a.
- Cdr1as's tumor-suppressive role is mediated through sponging multiple microRNAs, notably miR-135a.
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