Metabolic gene NR4A1 as a potential therapeutic target for non-smoking female non-small cell lung cancer patients.

Thoracic Cancer
Rong SunJin-Ku Bao

Abstract

Although cigarette smoking is considered one of the key risk factors for lung cancer, 15% of male patients and 53% of female patients with lung cancer are non-smokers. Metabolic changes are critical features of cancer. Therapeutic target identification from a metabolic perspective in non-small cell lung cancer (NSCLC) tissue of female non-smokers has long been ignored. Based on microarray data retrieved from Affymetrix expression arrays E-GEOD-19804, we found that the downregulated genes in non-smoking female NSCLC patients tended to participate in protein/amino acid and lipid metabolism, while upregulated genes were more involved in protein/amino acid and carbohydrate metabolism. Combining nutrient metabolic co-expression, protein-protein interaction network construction and overall survival assessment, we identified NR4A1 and TIE1 as potential therapeutic targets for NSCLC in female non-smokers. To accelerate the drug development for non-smoking female NSCLC patients, we identified nilotinib as a potential agonist targeting NR4A1 encoded protein by molecular docking and molecular dynamic stimulation. We also show that nilotinib inhibited proliferation and induced senescence of cells in non-smoking female NSCLC patients in vit...Continue Reading

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Datasets Mentioned

BETA
GSE31210

Methods Mentioned

BETA
X‐ray

Software Mentioned

Bioconductor
DAVID
AutoDock Vina
GraphPad Prism
GEOD
LigPlot
energy
Limma
UCSF Chimera
Dock6

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