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Updated: Jul 11, 2026
The Use of Reverse Phase Protein Arrays (RPPA) to Explore Protein Expression Variation within Individual Renal Cell Cancers
Published on: January 22, 2013
ATP5A1 as a potential prognostic biomarker in clear-cell renal cell carcinoma
Wei Zhou1,2, Qianli Tang3, Jun Wu2
1Graduate School of the First Clinical Medical College of Jinan University, Guangzhou, China.
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.
Insights
Adenosine triphosphate (ATP) synthase F1 subunit α (ATP5A1) is downregulated in clear cell renal cell carcinoma (ccRCC), promoting tumor progression. Lower ATP5A1 levels indicate a poorer prognosis, suggesting its potential as a ccRCC biomarker.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Clear cell renal cell carcinoma (ccRCC) presents challenges in treatment and outcomes.
- Mitochondrial ATP synthase F1 subunit α (ATP5A1) is crucial for tumor energy metabolism.
- The specific role and clinical significance of ATP5A1 in ccRCC remain underexplored.
Purpose of the Study:
- To investigate the function of ATP5A1 in ccRCC.
- To elucidate the molecular mechanisms underlying ATP5A1's role in ccRCC.
- To evaluate ATP5A1 as a potential diagnostic and prognostic biomarker for ccRCC.
Main Methods:
- Analysis of RNA sequencing data from The Cancer Genome Atlas (TCGA) for ccRCC.
- Validation of ATP5A1 expression using the Human Protein Atlas database.
- Functional characterization through in vitro assays: wound healing, transwell invasion, proliferation (CCK-8), and flow cytometry.
Main Results:
- ATP5A1 expression is significantly reduced in ccRCC tissues and cells compared to normal kidney tissues.
- Lower ATP5A1 levels correlate inversely with ccRCC clinical stage and grade, but positively with improved prognosis.
- ATP5A1 downregulation enhances ccRCC malignant behaviors and activates the Wnt/β-catenin pathway; upregulation inhibits these effects.
Conclusions:
- ATP5A1 downregulation promotes ccRCC progression by activating the Wnt/β-catenin pathway.
- ATP5A1 demonstrates potential as a diagnostic and prognostic biomarker for ccRCC.
- Targeting ATP5A1 may offer a novel therapeutic strategy for ccRCC.
