Adipose tissue inflammation and VDR expression and methylation in colorectal cancer

作者：Castellano Castillo Daniel; Morcillo Sonsoles; Clemente Postigo Mercedes^*; Belen Crujeiras Ana; Carlos Fernandez Garcia Jose; Torres Esperanza; Jose Tinahones Francisco; Macias Gonzalez Manuel

来源：Clinical Epigenetics, 2018, 10(1): 60.

DOI：10.1186/s13148-018-0493-0

• Vitamin D
• VDR
• DNA methylation
• Low-grade inflammation
• Colorectal cancer
• Adipose tissue

Background: Lack of vitamin D (VD) has been associated with colorectal cancer (CRC). VD has anti-inflammatory effects and regulates several cellular pathways by means of its receptor, including epigenetic modifications. Adipose tissue dysfunction has been related to low-grade inflammation, which is related to diseases like cancer. The aim of this study was to explore the relationship between serum 25-hydroxyvitamin D (25(OH) D), adipose tissue gene expression of VD receptor (VDR), pro-inflammatory markers, and the epigenetic factor DNA methyltransferase 3a (DNMT3A) as well as VDR promoter methylation in CRC.
Methods: Blood and visceral adipose tissue from 57 CRC and 50 healthy control subjects were collected. CRC subjects had lower serum 25(OH) D levels and higher VDR gene expression, and these were negatively correlated in the CRC group.
Results: Adipose tissue NF kappa B1, IL6, and IL1B gene expression were higher in the CRC subjects than in the control subjects. 25(OH) D correlated negatively with NF kappa B1 and CRP. In turn, CRP correlated positively with NF kappa B1, IL6, IL1B, and VDR gene expression as well as NF kappa B1 that correlated positively with IL6 and IL1B. DNMT3A mRNA was negatively correlated with serum 25(OH) D and positively correlated with VDR DNA methylation. VDR DNA methylation at position 4 had lower levels in the CRC group. Global NF kappa B1 methylation at dinucleotide 3 was lower in the CRC group.
Conclusion: Our results suggest that adipose tissue may be a key factor in CRC development. The low 25(OH) D levels and high adipose tissue VDR expression in CRC may, at least in part, mediate this relationship by modifying adipose tissue DNA methylation and promoting inflammation.

• 出版日期2018-4-25