ATP5A1 as a potential prognostic biomarker in clear-cell renal cell carcinoma.

Abstract

Background: Clear cell renal cell carcinoma (ccRCC), a malignant neoplasm originating in the renal tubules, is characterized by extended treatment durations and suboptimal therapeutic outcomes in clinical settings. Adenosine triphosphate (ATP) synthase F1 subunit α (ATP5A1), a subunit of mitochondrial ATP synthase, is integral to the energy metabolism of specific tumors. While prior research has established a link between ATP5A1 expression and malignancies, its precise function and clinical significance in ccRCC are yet to be elucidated. The study aims to investigate the role of ATP5A1 in ccRCC and to explore the underlying molecular mechanisms.

Methods: The RNA sequencing data from ccRCC and corresponding adjacent tissues were analyzed through The Cancer Genome Atlas to evaluate their diagnostic and prognostic implications. ATP5A1 expression in ccRCC was validated using the Human Protein Atlas database. The role of ATP5A1 in ccRCC was further characterized through a series of assays, including wound healing, transwell invasion, cell counting kit-8 proliferation, and flow cytometry.

Results: ATP5A1 expression levels were elevated across 17 tumor types while being notably downregulated in 15 others, including ccRCC, esophageal carcinoma, and colon adenocarcinoma. Compared to 293 cells and adjacent normal kidney tissues, renal cancer cells and tissues exhibited a significant reduction in ATP5A1 expression. An inverse relationship was observed between ATP5A1 expression and both the clinical stage and histological grade of ccRCC, yet it is positively associated with improved prognosis. Silencing ATP5A1 expression enhanced the malignant biological properties of ccRCC, while its upregulation inhibited these effects. Furthermore, ATP5A1 knockdown activated the Wnt/β-catenin signaling pathway, whereas its overexpression resulted in pathway suppression.

Conclusions: Collectively, this study indicates that ATP5A1 may serve as a potential biomarker for the diagnosis, prognosis, and therapeutic targeting of ccRCC.