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Updated: Jun 27, 2026

Overlapping Peptide Library to Map Qa-1 Epitopes in a Protein
Published on: December 20, 2017
AQP1 Suppresses Clear Cell Renal Cell Carcinoma via Epigenetic Silencing and TNF-Mediated Apoptosis
Shuo Pang1, Yingwei Bi1, Yuxin Liu1
1Department of Urology, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China.
Abstract:
Clear cell renal cell carcinoma (ccRCC) is notorious for its clinical unpredictability. While Aquaporin-1 (AQP1) is a major water channel in healthy kidneys, its specific role and regulatory mechanisms in ccRCC remain unclear. Using bioinformatics analysis of 610 TCGA-KIRC patients (RNA sequencing and DNA methylation), single-cell transcriptomics of 27,402 cells, and experimental validation (CCK-8, scratch, Transwell, and xenograft assays, with Western blotting, HE staining, and immunohistochemistry), we systematically characterized AQP1 expression, regulation, and function. AQP1 was significantly downregulated in ccRCC via promoter hypermethylation, with single-cell analysis confirming tumor cell-specific loss. Low AQP1 correlated with worse prognosis; multivariate Cox regression identified AQP1 as an independent protective factor (HR = 0.510, p < 0.001), and a prognostic nomogram showed good predictive accuracy for 1-, 3-, and 5-year survival. AQP1 overexpression suppressed proliferation, migration, invasion, and xenograft growth, accompanied by upregulation of TNF-α, TNFRSF1A, Bax, and Cleaved Caspase-3 and reduced Vimentin, suggesting activation of TNF-related pro-apoptotic signaling. AQP1 is epigenetically silenced in ccRCC and suppresses tumor growth via TNF-mediated apoptosis, establishing it as an independent prognostic biomarker and candidate therapeutic target.
Insights
Aquaporin-1 (AQP1) is epigenetically silenced in clear cell renal cell carcinoma (ccRCC), suppressing tumor growth. AQP1 acts as a protective prognostic biomarker and potential therapeutic target in ccRCC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Clear cell renal cell carcinoma (ccRCC) exhibits clinical unpredictability.
- The role and regulation of Aquaporin-1 (AQP1), a major kidney water channel, in ccRCC are not well understood.
Purpose of the Study:
- To systematically characterize AQP1 expression, epigenetic regulation, and functional role in ccRCC.
- To evaluate AQP1 as a prognostic biomarker and potential therapeutic target in ccRCC.
Main Methods:
- Bioinformatics analysis of 610 TCGA-KIRC patient data (RNA sequencing, DNA methylation).
- Single-cell transcriptomics of 27,402 cells.
- Experimental validation including cell-based assays (CCK-8, scratch, Transwell) and xenograft models, with molecular analyses (Western blotting, HE staining, immunohistochemistry).
Main Results:
- AQP1 was significantly downregulated in ccRCC due to promoter hypermethylation, with tumor cell-specific loss confirmed by single-cell analysis.
- Low AQP1 expression correlated with poorer prognosis and was identified as an independent protective factor (HR = 0.510, p < 0.001).
- AQP1 overexpression inhibited ccRCC cell proliferation, migration, invasion, and xenograft growth, activating TNF-related pro-apoptotic signaling.
Conclusions:
- AQP1 is epigenetically silenced in ccRCC and functions as a tumor suppressor by promoting TNF-mediated apoptosis.
- AQP1 serves as an independent prognostic biomarker with good predictive accuracy for ccRCC patient survival.
- AQP1 represents a promising candidate for therapeutic targeting in ccRCC.
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