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Transcriptomic analysis unveils correlations between regulative apoptotic caspases and genes of cholesterol

Raffaella Picco1, Andrea Tomasella1, Federico Fogolari1

  • 1Department of Medical and Biological Sciences, Università degli Studi di Udine, Udine, Italy.

Plos One
|October 21, 2014
PubMed

Insights

Caspase-2 silencing affects cholesterol homeostasis genes in glioblastoma. Apoptotic and inflammatory caspases link to cholesterol genes in the brain, impacting Glioblastoma Multiforme and potentially brain aging.

Area of Science:

  • Molecular Biology
  • Neuroscience
  • Genetics

Background:

  • Gene expression is regulated by interconnected circuits that coordinate gene function and compensate for network disruptions.
  • Caspases, cysteine-proteases, are critical for apoptosis execution.
  • Dysregulation of caspase-2 impacts gene expression, including genes involved in cholesterol homeostasis.

Purpose of the Study:

  • To investigate the relationship between caspase expression and cholesterol homeostasis genes.
  • To explore the tissue specificity of these correlations.
  • To determine the potential link to Glioblastoma Multiforme (GBM) and brain aging.

Main Methods:

  • Silencing of caspase-2 in glioblastoma cell lines.
  • Analysis of Lysosomal Acid Lipase A (LIPA) expression and cellular cholesterol staining.
  • Large-scale mRNA expression analysis and hierarchical clustering of caspases and cholesterol homeostasis genes in brain and liver tissues.

Main Results:

  • Down-regulation of caspase-2 led to up-regulation of cholesterol homeostasis genes and reduced cholesterol in lipid droplets.
  • In the brain, apoptotic caspases (CASP2, CASP8, CASP9, CASP10) and inflammatory CASP1 expression correlate with cholesterol homeostasis genes.
  • These correlations are tissue-specific, differing between brain and liver, and CASP1 shows a significant link to Glioblastoma Multiforme (GBM).

Conclusions:

  • Caspase expression is interconnected with cholesterol homeostasis pathways, particularly in the brain.
  • CASP1's correlation with cholesterol genes is notably linked to Glioblastoma Multiforme (GBM).
  • Some caspase-cholesterol gene correlations may be associated with brain aging.

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