Department of Vascular Surgery, Renji Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, 200127, China.
Department of Biomedical Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, Maryland, USA.
World J Urol. 2024 Oct 30;42(1):607. doi: 10.1007/s00345-024-05279-5.
This study explores the role of circular RNA derived from the Multidrug Resistance Protein 4 (MRP4/ABCC4) gene, which is markedly elevated in renal cell carcinoma (RCC). Our objective is to clarify how this circular RNA contributes to the progression and development of RCC.
We quantified the presence of circular ABCC4 RNA in tissue samples, plasma and urine from patients diagnosed with RCC. In addition, the impact of this circular RNA on RCC tumour growth was assessed through studies in RCC cell lines and in animal models mimicking the disease.
Our findings reveal that circular ABCC4 RNA, specifically the variant containing exons 25-29 (circABCC4e), is upregulated in RCC cell lines and tissues. This upregulation correlates with advanced tumor stages in RCC patients, suggesting circABCC4e's potential as a biomarker for RCC progression. Furthermore, the reduction in circABCC4e levels following tumor resection indicates its potential utility in monitoring treatment response. The mechanism by which circABCC4e promotes RCC tumor growth through the antagonism of tumor-suppressive microRNAs highlights its significance in RCC pathogenesis. These insights may inform the development of diagnostic and therapeutic strategies for RCC.
This study demonstrates that circABCC4e accelerates RCC progression by inhibiting tumor-suppressive microRNAs. Its role as a diagnostic and prognostic biomarker for RCC underscores its potential value in improving RCC management.
本研究探讨了多药耐药蛋白 4（MRP4/ABCC4）基因衍生的环状 RNA 的作用，该环状 RNA 在肾细胞癌（RCC）中显著升高。我们的目的是阐明这种环状 RNA 如何促进 RCC 的进展和发展。
我们定量检测了 RCC 患者组织样本、血浆和尿液中环状 ABCC4 RNA 的存在。此外，通过 RCC 细胞系和模拟疾病的动物模型研究评估了这种环状 RNA 对 RCC 肿瘤生长的影响。
我们的研究结果表明，环状 ABCC4 RNA，特别是包含外显子 25-29 的变体（circABCC4e），在 RCC 细胞系和组织中上调。这种上调与 RCC 患者的晚期肿瘤阶段相关，表明 circABCC4e 可能作为 RCC 进展的生物标志物。此外，肿瘤切除后 circABCC4e 水平的降低表明其在监测治疗反应方面的潜在用途。circABCC4e 通过拮抗肿瘤抑制性 microRNAs 促进 RCC 肿瘤生长的机制突出了其在 RCC 发病机制中的重要性。这些见解可能为 RCC 的诊断和治疗策略的发展提供信息。
本研究表明，circABCC4e 通过抑制肿瘤抑制性 microRNAs 加速 RCC 进展。其作为 RCC 的诊断和预后生物标志物，凸显了其在改善 RCC 管理方面的潜在价值。
