Circular RNA circAGAP1 promotes sunitinib sensitivity in renal cell carcinoma via sponging multiple PDGFR-targeted miRNAs

被引：1

作者：

Lv, Qi ^{[1
]}

Wang, Gangmin ^{[2
]}

Hong, Yi ^{[1
]}

Zhu, Tianyi ^{[1
]}

Qin, Shuang ^{[1
]}

Sun, Saifei ^{[1
]}

Wang, Yuting ^{[1
]}

Liu, Yaohua ^{[1
]}

Zhang, Qing ^{[1
]}

Ma, Chunhui ^{[3
]}

Wang, Peijun ^{[1
]}

机构：

[1] Tongji Univ, Tongji Hosp, Imaging Dept, Sch Med, Shanghai 200065, Peoples R China

[2] Fudan Univ, Huashan Hosp, Urol Dept, Shanghai 200040, Peoples R China

[3] Shanghai Jiao Tong Univ, Orthoped Dept, Shanghai Gen Hosp, Shanghai 200080, Peoples R China

来源：

ONCOLOGY RESEARCH | 2025年 / 33卷 / 02期

基金：

中国国家自然科学基金;

关键词：

Renal cell carcinoma; Sunitinib resistance; Circular RNA circAGAP1; MiR-149-5p; MiR-455-5p; MiR-15a-5p;

D O I：

10.32604/or.2024.047698

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：407 / 420

页数：14