Circ-PGPEP1 augments renal cell carcinoma proliferation, Warburg effect, and distant metastasis

  • PeiRui Wang Department of Urology, Affiliated Hospital of Zunyi Medical University, Zunyi City, Guizhou Province, 563000, China
  • Jin Chen Department of Pediatric Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi City, Guizhou Province, 563000, China
  • Xin Ye Department of Urology, Institute of Urology, West China Hospital of Sichuan University, Chengdu City, Sichuan Province, 610000, China
  • RuYi Wang Department of Urology, Affiliated Hospital and Clinical Medical College of Chengdu University, Chengdu City, Sichuan Province, 610081, China
  • Lin Chen Department of Urology, Affiliated Hospital and Clinical Medical College of Chengdu University, Chengdu City, Sichuan Province, 610081, China
  • HanChao Zhang Department of Urology, Affiliated Hospital and Clinical Medical College of Chengdu University, Chengdu City, Sichuan Province, 610081, China https://orcid.org/0000-0001-5285-2668

Abstract

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.

Published
2023-09-18
Section
Articles