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Updated: May 30, 2025

Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
Circular RNA circAGAP1 promotes sunitinib sensitivity in renal cell carcinoma via sponging multiple PDGFR-targeted
Q I Lv1, Gangmin Wang2, Y I Hong1
1Imaging Department, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.
Background:
Sunitinib resistance is a major challenge in advanced renal cell carcinoma (RCC). Clinically, elucidating the underlying mechanisms and developing practical countermeasures for sunitinib resistance in RCC is desirable. In previous studies, we found that circAGAP1 expression was significantly upregulated in clear cell RCC (ccRCC) and was strongly associated with poor prognosis. However, the role of circAGAP1 in sunitinib resistance in ccRCC remains unclear.
Methods:
We used public databases for bioinformatics analysis to identify the binding targets of circAGAP1. Additionally, the effects of circAGAP1 on the proliferation, clonogenesis, apoptosis, and migration of ccRCC cells were analyzed using quantitative real-time PCR, cell counting kit-8 assays, migration and apoptosis assays, and colony formation assays. Furthermore, RNA immunoprecipitation, dual-luciferase reporter, and fluorescence in situ hybridization assays were used to explore the molecular mechanism.
Results:
In this study, circAGAP1 exhibited higher expression in sunitinib-sensitive ccRCC cells and inhibited the clonogenesis, proliferation, and migration of ccRCC cells after sunitinib treatment. Mechanical studies revealed that circAGAP1 regulated the expression of sunitinib target platelet-derived growth factor receptor by acting as a microRNA sponge that suppresses miR-149-5p, miR-455-5p, and miR-15a-5p simultaneously. Overexpression of these three miRNAs reversed circAGAP1-mediated sunitinib sensitivity in ccRCC.
Conclusions:
In summary, our findings indicate that circAGAP1 may serve as a promising biomarker to predict sunitinib sensibility and a therapeutic target in ccRCC.
Insights
Circular RNA circAGAP1 enhances sunitinib sensitivity in clear cell renal cell carcinoma (ccRCC). This finding suggests circAGAP1 is a potential biomarker and therapeutic target for ccRCC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Sunitinib resistance is a significant clinical challenge in advanced renal cell carcinoma (RCC).
- Previous studies identified circAGAP1 upregulation in clear cell RCC (ccRCC) associated with poor prognosis.
- The role of circAGAP1 in sunitinib resistance in ccRCC was previously unclear.
Purpose of the Study:
- To investigate the role of circAGAP1 in sunitinib resistance in clear cell renal cell carcinoma.
- To elucidate the underlying molecular mechanisms of circAGAP1 in ccRCC sunitinib resistance.
- To evaluate circAGAP1 as a potential biomarker and therapeutic target for ccRCC.
Main Methods:
- Bioinformatics analysis of public databases to identify circAGAP1 binding targets.
- In vitro assays (qPCR, CCK-8, migration, apoptosis, colony formation) to assess circAGAP1 effects on ccRCC cells.
- RNA immunoprecipitation, dual-luciferase reporter, and FISH assays to explore molecular mechanisms.
Main Results:
- circAGAP1 expression was higher in sunitinib-sensitive ccRCC cells and inhibited proliferation, clonogenesis, and migration post-sunitinib treatment.
- circAGAP1 acts as a microRNA sponge, suppressing miR-149-5p, miR-455-5p, and miR-15a-5p to regulate sunitinib target platelet-derived growth factor receptor.
- Overexpression of these three miRNAs reversed circAGAP1-mediated sunitinib sensitivity.
Conclusions:
- circAGAP1 demonstrates a role in enhancing sunitinib sensitivity in ccRCC.
- circAGAP1 functions by sponging specific microRNAs, impacting ccRCC cell behavior under sunitinib treatment.
- circAGAP1 is a potential predictive biomarker for sunitinib sensitivity and a therapeutic target in ccRCC.
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