Department of Urology, Affiliated Hospital of Zunyi Medical University, Zunyi City, Guizhou Province, 563000, China.
Department of Pediatric Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi City, Guizhou Province, 563000, China.
Acta Biochim Pol. 2023 Sep 18;70(3):703-711. doi: 10.18388/abp.2020_6511.
Circular RNAs (circRNAs) contribute to the malignant phenotype and progression of several types of human cancers, including renal cell carcinoma (RCC). This study probed the molecular mechanism of circPGPEP1 regulating RCC proliferation, Warburg effect, and distant metastasis by targeting the miR-378a-3p/JPT1 axis. Here identified higher circPGPEP1 expression in RCC tissues and cells by RT-qPCR, and high levels of circPGPEP1 were positively correlated with high histological grade and distant metastasis in RCC patients. Furthermore, patients with high levels of circPGPEP1 had a worse survival prognosis. Functional assays presented that knockdown of circPGPEP1 inhibited RCC proliferation, invasion, migration, EMT, and Warburg effect. Dual-luciferase reporter assay, RNA immunoprecipitation, nucleoplasmic RNA isolation, and functional rescue experiments confirmed that circPGPEP1 induced JPT1 expression by sponging miR-378a-3p, thereby promoting RCC malignant phenotype. Xenograft assays and metastasis models further demonstrated that down-regulation of circPGPEP1 effectively inhibited tumor growth and distant metastasis of RCC. Taken together, circPGPEP1, a prognostic circRNA in RCC, acts through the miR-378a-3p/JPT1 axis to regulate RCC progression.
环状 RNA（circRNAs）有助于多种人类癌症的恶性表型和进展，包括肾细胞癌（RCC）。本研究通过靶向 miR-378a-3p/JPT1 轴，探讨 circPGPEP1 调控 RCC 增殖、Warburg 效应和远处转移的分子机制。通过 RT-qPCR 鉴定发现，RCC 组织和细胞中 circPGPEP1 的表达较高，且 RCC 患者中 circPGPEP1 水平较高与高组织学分级和远处转移呈正相关。此外，circPGPEP1 水平较高的患者生存预后较差。功能测定表明，circPGPEP1 的敲低抑制了 RCC 的增殖、侵袭、迁移、EMT 和 Warburg 效应。双荧光素酶报告基因检测、RNA 免疫沉淀、核质 RNA 分离和功能恢复实验证实，circPGPEP1 通过海绵吸附 miR-378a-3p 诱导 JPT1 表达，从而促进 RCC 恶性表型。异种移植实验和转移模型进一步表明，下调 circPGPEP1 可有效抑制 RCC 的肿瘤生长和远处转移。总之，circPGPEP1 是 RCC 中的一种预后环状 RNA，通过 miR-378a-3p/JPT1 轴调节 RCC 进展。
