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PPARgamma-mediated ALDH1A3 suppression exerts anti-proliferative effects in lung cancer by inducing lipid

Tuyen N M Hua1,2, Jun Namkung1, Ai N H Phan1,2

  • 1a Department of Biochemistry, Wonju College of Medicine , Yonsei University , Wonju , South Korea.

Journal of Receptor and Signal Transduction Research
|June 7, 2018
PubMed
Abstract

Insights

Peroxisome proliferator-activated receptor gamma (PPARγ) activation suppresses aldehyde dehydrogenase 1A3 (ALDH1A3) expression, inhibiting lung cancer cell growth and increasing lipid peroxidation. This suggests PPARγ has a tumor-suppressive role in lung cancer.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • The role of peroxisome proliferator-activated receptor gamma (PPARγ) in lung cancer metabolism is not well understood.
  • Investigating PPARγ's function is crucial for developing new lung cancer therapies.

Purpose of the Study:

  • To elucidate the relationship between PPARγ and aldehyde dehydrogenase 1A3 (ALDH1A3) in lung cancer.
  • To determine how PPARγ influences ALDH1A3-induced lipid peroxidation and lung cancer cell proliferation.

Main Methods:

  • In silico analysis of microarray data to identify correlations between PPARγ and ALDH isoforms.
  • ChIP assay and NUBIscan software to pinpoint PPARγ binding sites on the ALDH1A3 promoter.
  • Quantitative PCR, Western Blot, and colony formation assays to assess gene expression, protein levels, cell growth, and lipid peroxidation (4-hydroxy-2-nonenal).

Main Results:

  • ALDH1A3 demonstrated the strongest positive correlation with PPARγ expression among all ALDH isoforms.
  • PPARγ directly bound to a specific site (BS2) on the ALDH1A3 promoter, suppressing its mRNA and protein expression.
  • PPARγ activation inhibited lung cancer cell growth and increased lipid peroxidation marker 4-hydroxy-2-nonenal (4HNE) in PPARγ-positive cells.

Conclusions:

  • Aldehyde dehydrogenase 1A3 (ALDH1A3) suppression is a potential mechanism for the tumor-suppressive function of PPARγ in lung cancer.
  • This research enhances the understanding of PPARγ's multifaceted role in lung cancer progression and provides a basis for targeted therapeutic strategies.
Keywords:
ALDH1A3PPARgammalung cancer

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