[Abnormal expression of genes that regulate retinoid metabolism and signaling in non-small-cell lung cancer]

Mol Biol (Mosk). 2016 Mar-Apr;50(2):255-65. doi: 10.7868/S0026898416020130.
[Article in Russian]

Abstract

Retinoids are signaling molecules that control a wide variety of cellular processes and possess antitumor activity. This work presents a comprehensive description of changes in the expression of 23 genes that regulate retinoid metabolism and signaling in non-small-cell lung cancer tumors compared to adjacent normal tissues obtained using RT-PCR. Even at early stages of malignant transformation, a significant decrease in ADH1B, ADH3, RDHL, and RALDH1 mRNA levels was observed in 82, 79, 73, and 64% of tumor specimens, respectively, and a considerable increase in AKR1B10 mRNA content was observed in 80% of tumors. Dramatic changes in the levels of these mRNAs can impair the synthesis of all-trans retinoic acid, a key natural regulatory retinoid. Apart from that, it was found that mRNA levels of nuclear retinoid receptor genes RXRγ, RARα, RXRα, and gene RDH11 were significantly decreased in 80, 67, 57, and 66% of tumor specimens, respectively. Thus, neoplastic transformation of lung tissue cells is accompanied with deregulated expression of key genes of retinoid metabolism and function.

Keywords: biosynthesis of retinoic acid; gene expression; nonsmall-cell lung cancer; retinoid metabolism; retinoid receptor genes.

MeSH terms

  • 3-Hydroxysteroid Dehydrogenases / biosynthesis*
  • 3-Hydroxysteroid Dehydrogenases / genetics
  • Alcohol Dehydrogenase / biosynthesis*
  • Alcohol Dehydrogenase / genetics
  • Aldehyde Dehydrogenase / biosynthesis*
  • Aldehyde Dehydrogenase / genetics
  • Aldehyde Dehydrogenase 1 Family
  • Aldehyde Reductase / biosynthesis*
  • Aldehyde Reductase / genetics
  • Aldo-Keto Reductases
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Transformation, Neoplastic / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • RNA, Messenger / biosynthesis
  • Receptors, Retinoic Acid / biosynthesis
  • Receptors, Retinoic Acid / genetics
  • Retinal Dehydrogenase
  • Retinoic Acid Receptor alpha
  • Retinoids / genetics
  • Retinoids / metabolism
  • Signal Transduction / genetics
  • Tretinoin / metabolism

Substances

  • RARA protein, human
  • RNA, Messenger
  • Receptors, Retinoic Acid
  • Retinoic Acid Receptor alpha
  • Retinoids
  • Tretinoin
  • 3-Hydroxysteroid Dehydrogenases
  • DHRS9 protein, human
  • AKR1B10 protein, human
  • Aldo-Keto Reductases
  • ADH1B protein, human
  • ADH1C protein, human
  • Alcohol Dehydrogenase
  • Aldehyde Reductase
  • Aldehyde Dehydrogenase 1 Family
  • Aldehyde Dehydrogenase
  • ALDH1A1 protein, human
  • Retinal Dehydrogenase