Correlated downregulation of VDR and CYP3A4 in colorectal cancer

Mol Biol Rep. 2023 Feb;50(2):1385-1391. doi: 10.1007/s11033-022-08141-2. Epub 2022 Dec 5.

Abstract

Background: The evidence obtained from experimental studies suggests the tumor-suppressive effects of vitamin D by controlling the differentiation, proliferation, and apoptosis in cancerous cells. Furthermore, the deregulation of genes involved in vitamin D metabolism has been reported in several types of cancer.

Methods: In the present study, we investigated the expression level of vitamin D metabolic pathway genes, including VDR, CYP3A4, RXRα, and GC, in colorectal cancer (CRC) samples compared with the adjacent tissues by using quantitative RT-PCR.

Results: The results indicated significant downregulation of CYP3A4 and VDR genes in CRC tissues compared with the adjacent control tissues (p < 0.01). RXRA and GC expression levels did not show any significant alteration among the studied samples. Moreover, a positive correlation was observed between the expression level of CYP3A4 and VDR genes (p < 0.0001). ROC curve analysis also revealed the potential diagnostic power of CYP3A4 and VDR genes in CRC samples.

Conclusion: Reduction in the expression of both CYP3A4 and VDR plays an important role in CRC due to the possible impairment in vitamin D metabolism. Further studies concerning the relationship between the expression of these genes and colorectal cancer pathogenesis and treatment are recommended.

Keywords: CYP3A4; Colorectal cancer; Expression; GC; RXRα; VDR; Vitamin D.

MeSH terms

  • Colorectal Neoplasms* / metabolism
  • Cytochrome P-450 CYP3A / genetics
  • Cytochrome P-450 CYP3A / metabolism
  • Down-Regulation / genetics
  • Humans
  • Receptors, Calcitriol* / genetics
  • Receptors, Calcitriol* / metabolism
  • Vitamin D / genetics
  • Vitamin D / metabolism
  • Vitamins

Substances

  • Receptors, Calcitriol
  • Cytochrome P-450 CYP3A
  • Vitamin D
  • Vitamins
  • CYP3A4 protein, human
  • VDR protein, human