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.

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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