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Updated: Jun 22, 2025
Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane
Published on: February 8, 2020
Exploring the oncogenic potential of circSOD2 in clear cell renal cell carcinoma: a novel positive feedback loop
Gao-Sheng Yao1, Liang-Min Fu1, Jun-Shang Dai2,3
1Department of Urology, The First Affiliated Hospital of Sun Yat-Sen University, No. 58, ZhongShan 2nd Road, Guangzhou, 510080, Guangdong, China.
Background:
Existing studies have found that circular RNAs (circRNAs) act as sponges for micro RNAs (miRNAs) to control downstream genes. However, the specific functionalities and mechanisms of circRNAs in human clear cell renal cell carcinoma (ccRCC) have yet to be thoroughly investigated.
Methods:
Patient cohorts from online databases were used to screen candidate circRNAs, while another cohort from our hospital was obtained for validation. CircSOD2 was identified as a potential oncogenic target, and its relevant characteristics were investigated during ccRCC progression through various assays. A positive feedback loop containing downstream miRNA and its target gene were identified using bioinformatics and validated by luciferase reporter assays, RNA pull-down, and high-throughput sequencing.
Results:
CircSOD2 expression was elevated in tumor samples and significantly correlated with overall survival (OS) and the tumor stage of ccRCC patients, which appeared in the enhanced proliferation, invasion, and migration of tumor cells. Through competitive binding to circSOD2, miR-532-3p can promote the expression of PAX5 and the progression of ccRCC, and such regulation can be salvaged by miR-532-3p inhibitor.
Conclusion:
A novel positive feedback loop, PAX5/circSOD2/miR-532-3p/PAX5 was identified in the study, indicating that the loop may play an important role in the diagnosis and prognostic prediction in ccRCC patients.
Insights
Circular RNAs (circRNAs) like CircSOD2 are elevated in clear cell renal cell carcinoma (ccRCC), promoting tumor progression. A novel PAX5/circSOD2/miR-532-3p/PAX5 feedback loop is identified, offering diagnostic and prognostic potential for ccRCC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Circular RNAs (circRNAs) regulate gene expression by sponging microRNAs (miRNAs).
- The specific roles of circRNAs in human clear cell renal cell carcinoma (ccRCC) remain largely unexplored.
Purpose of the Study:
- To investigate the function and mechanism of circRNAs in ccRCC progression.
- To identify novel circRNAs involved in ccRCC pathogenesis.
Main Methods:
- Screening and validation of candidate circRNAs using patient cohorts.
- Functional assays to assess the role of CircSOD2 in ccRCC.
- Bioinformatic analysis and experimental validation of miRNA-target interactions.
Main Results:
- CircSOD2 expression is upregulated in ccRCC tissues and correlates with poor overall survival and advanced tumor stage.
- CircSOD2 promotes ccRCC cell proliferation, invasion, and migration.
- A positive feedback loop involving PAX5, circSOD2, and miR-532-3p was identified, promoting ccRCC progression.
Conclusions:
- A novel oncogenic feedback loop (PAX5/circSOD2/miR-532-3p/PAX5) is identified in ccRCC.
- This loop plays a significant role in ccRCC pathogenesis.
- The identified feedback loop holds potential for ccRCC diagnosis and prognostic prediction.
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