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Published on: March 14, 2019
Correlated downregulation of VDR and CYP3A4 in colorectal cancer
Hossein Sadeghi1, Veys Hashemnia2, Ehsan Nazemalhosseini-Mojarad3
1Genomic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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.
Insights
Vitamin D receptor (VDR) and CYP3A4 gene expression are significantly reduced in colorectal cancer (CRC). This downregulation may impair vitamin D metabolism and contribute to CRC development, suggesting diagnostic potential.
Area of Science:
- Molecular biology
- Cancer research
- Endocrinology
Background:
- Vitamin D exhibits tumor-suppressive properties by regulating cell differentiation, proliferation, and apoptosis.
- Aberrant expression of vitamin D metabolism genes is implicated in various cancers.
Purpose of the Study:
- To investigate the expression levels of vitamin D metabolic pathway genes (VDR, CYP3A4, RXRα, GC) in colorectal cancer (CRC) tissues versus adjacent normal tissues.
- To assess the diagnostic potential of these genes in CRC.
Main Methods:
- Quantitative reverse transcription polymerase chain reaction (RT-PCR) was employed to measure gene expression.
- Comparison of gene expression between CRC samples and adjacent non-cancerous tissues.
- Receiver Operating Characteristic (ROC) curve analysis was performed.
Main Results:
- Significant downregulation of CYP3A4 and VDR gene expression was observed in CRC tissues compared to adjacent tissues (p < 0.01).
- No significant alteration in RXRA and GC expression levels was found.
- A strong positive correlation between CYP3A4 and VDR expression (p < 0.0001) and diagnostic potential for CYP3A4 and VDR were identified.
Conclusions:
- Reduced expression of CYP3A4 and VDR is linked to colorectal cancer, potentially through impaired vitamin D metabolism.
- Further research is warranted to explore the role of these genes in CRC pathogenesis and therapeutic strategies.
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