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Published on: November 19, 2019

PPARγ disease gene network and identification of therapeutic targets for prostate cancer

Gireedhar Venkatachalam1, Alan Prem Kumar, Kishore R Sakharkar

  • 1Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

Journal of Drug Targeting
|July 26, 2011
PubMed

Insights

This study computationally identified PPARγ target genes, revealing their association with diseases like cancer. Two key genes, PRKCZ and PGK1, were validated as potential therapeutic targets for prostate cancer.

Area of Science:

  • Molecular Biology
  • Genomics
  • Systems Biology

Background:

  • Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear hormone receptor.
  • PPARγ response elements include direct repeat 1 (DR1) and direct repeat 2 (DR2) sequences.
  • A systematic approach to construct PPARγ disease-specific gene networks is needed.

Purpose of the Study:

  • To computationally identify PPARγ direct target genes.
  • To construct a PPARγ disease gene network incorporating DR1 and DR2 elements.
  • To identify novel therapeutic targets for PPARγ-associated diseases, particularly prostate cancer.

Main Methods:

  • Computational identification of 1154 PPARγ direct target genes.
  • Construction of a PPARγ disease gene network.
  • Experimental validation of PRKCZ and PGK1 repression in prostate cancer cell lines upon PPARγ activation.

Main Results:

  • Identified 1154 PPARγ direct target genes.
  • Constructed a network revealing 138 PPARγ target genes linked to 65 diseases, predominantly cancer and neurological disorders.
  • Validated PRKCZ and PGK1 as repressed PPARγ target genes in prostate cancer, suggesting their therapeutic potential.

Conclusions:

  • PPARγ plays a significant role in regulating genes associated with cancer and neurological diseases.
  • PRKCZ and PGK1 are proposed as novel therapeutic targets for prostate cancer.
  • This study provides a foundation for understanding PPARγ's role in disease and identifying new gene targets.

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