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Updated: Nov 16, 2025

Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane
Published on: February 8, 2020
CircAGAP1 promotes tumor progression by sponging miR-15-5p in clear cell renal cell carcinoma
Qi Lv1, Gangmin Wang2, Yinan Zhang3
1Department of Medical Imaging, Tongji Hospital, Tongji University School of Medicine, Xincun Road No. 389, Shanghai, China.
Background:
Accumulating evidence has revealed that circular RNAs (circRNAs), as novel noncoding RNAs, play critical roles in carcinogenesis and tumor progression. However, the functions and molecular mechanisms of circRNAs in clear cell renal cell carcinoma (ccRCC) are largely unknown.
Methods:
The expression and functions of circAGAP1 were identified in clinical samples, ccRCC cells and in vivo animal models. The molecular mechanism of circAGAP1 was investigated by fluorescence in situ hybridization, RNA immunoprecipitation and luciferase assays.
Results:
circAGAP1 (circ0058792) expression was significantly upregulated in ccRCC tissues compared to adjacent nontumor tissues. Moreover, the expression of circAGAP1 was closely related to the tumor size, nuclear grade and clinical stage of ccRCC in patients. Mechanistic studies demonstrated that cytoplasmic circAGAP1 targeted miR-15-5p in an RNA-induced silencing complex. Additionally, miR-15-5p expression was downregulated in ccRCC. Luciferase reporter assays showed that E2F transcription factor 3 (E2F3) was a target of miR-15-5p, and upregulated E2F3 expression was positively correlated with circAGAP1 in ccRCC. Furthermore, the tumor-promoting functions of circAGAP1 could be alleviated by miR-15-5p mimics in vitro and in vivo.
Conclusion:
Our results clarify that circAGAP1 exerts its oncogenic functions as a competitive endogenous RNA (ceRNA) by sponging miR-15-5p, which promotes E2F3 expression. Targeting circAGAP1 might be a new attractive therapeutic strategy in ccRCC.
Insights
Circular RNA AGAP1 (circAGAP1) is upregulated in clear cell renal cell carcinoma (ccRCC), promoting tumor growth by sponging miR-15-5p and increasing E2F3 expression. Targeting circAGAP1 offers a potential therapeutic strategy for ccRCC.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Circular RNAs (circRNAs) are emerging as key regulators in cancer development.
- The specific roles of circRNAs in clear cell renal cell carcinoma (ccRCC) remain largely unexplored.
Purpose of the Study:
- To investigate the expression, function, and molecular mechanism of circAGAP1 in ccRCC.
- To explore the potential of circAGAP1 as a therapeutic target in ccRCC.
Main Methods:
- Quantitative analysis of circAGAP1 expression in ccRCC tissues and cell lines.
- In vitro and in vivo functional assays to determine circAGAP1's role.
- Molecular mechanism studies including RNA immunoprecipitation and luciferase assays to elucidate interactions with miR-15-5p and E2F3.
Main Results:
- circAGAP1 expression is significantly upregulated in ccRCC and correlates with tumor progression.
- circAGAP1 acts as a molecular sponge for miR-15-5p, leading to decreased miR-15-5p levels.
- circAGAP1 promotes ccRCC progression by upregulating E2F3 expression via sponging miR-15-5p.
Conclusions:
- circAGAP1 functions as an oncogenic circRNA in ccRCC through the miR-15-5p/E2F3 axis.
- circAGAP1 may serve as a novel biomarker and therapeutic target for ccRCC.
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