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HADH suppresses clear cell renal cell carcinoma progression through reduced NRF2-dependent glutathione synthesis

Changbin Chu1, Shangjing Liu2, Zhiting He2

  • 1Institute of Life Sciences, Chongqing Medical University, Chongqing, 400016, China; Department of Urology, Chongqing Red Cross Hospital (People's Hospital of Jiangbei District), Chongqing, 400020, China.

Translational Oncology
|September 3, 2024
PubMed
Abstract

Insights

Hydroxyacyl dehydrogenases (HADH) suppresses clear cell renal cell carcinoma (ccRCC) progression by reducing glutathione synthesis via NRF2 inhibition. Low HADH expression indicates a poor prognosis for ccRCC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Clear cell renal cell carcinoma (ccRCC) poses a significant health risk, necessitating research into its pathogenesis.
  • Understanding the role of hydroxyacyl dehydrogenases (HADH) in ccRCC progression is crucial for developing effective treatments.

Purpose of the Study:

  • To evaluate the clinical significance of HADH in ccRCC.
  • To investigate the mechanism by which HADH influences ccRCC malignant progression.

Main Methods:

  • Bioinformatic analysis of HADH expression and prognosis.
  • Experimental validation using RT-PCR, Western blot, and immunohistochemistry.
  • Functional assays including cell proliferation, apoptosis, migration, invasion, and xenograft models.
  • Metabolomic analysis and NRF2 pathway investigation.

Main Results:

  • HADH expression is significantly decreased in ccRCC tissues, correlating with poor prognosis.
  • Overexpression of HADH inhibits ccRCC cell proliferation, migration, and invasion.
  • HADH overexpression reduces glutathione (GSH) synthesis and induces oxidative stress.
  • NRF2 activation counteracts the inhibitory effects of HADH overexpression.

Conclusions:

  • HADH suppresses ccRCC malignancy by attenuating GSH synthesis through inhibition of NRF2 nuclear translocation.
  • HADH represents a potential novel therapeutic target for ccRCC treatment.
Keywords:
Clear cell renal cell carcinomaGlutathione synthesisHADHNRF2Non-target metabolomics

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