Assessment of Functional Variants and Expression of Long Noncoding RNAs in Vitamin D Receptor Signaling in Breast Cancer

Purpose: Vitamin D receptor (VDR) signaling pathway is implicated in the pathogenesis of breast cancer.

Patients And Methods: We selected VDR-associated long noncoding RNAs (lncRNAs) through an in silico analysis of available microarray and RNA-sequencing data and assessed their expression in 75 breast tumor samples and their adjacent noncancerous tissues (ANCTs). We also genotyped two functional polymorphisms within gene in all patients.

Results: , , and were significantly upregulated in tumoral tissues compared with ANCTs (fold change [FC] =1.85, =0.03; =1.54, =0.04; and =4.75, =0.000, respectively). In patients younger than 55 years, significant associations were found between expression levels of both and genes and nuclear grade (=0.03), expression of and tubule formation (=0.01), expression of both and genes and family history of cancer (=0.01 and 0.03, respectively), as well as expression of and progesterone receptor status (=0.03). We detected significant correlations between expression levels of and in both tumoral tissues and ANCTs. The TT genotype of FokI polymorphism was associated with the higher expression levels of . FokI variants were associated with expression levels of both and in ANCTs (=0.01 and 0.03, respectively). CdxII variants were associated with expression levels of in ANCTs. A significant correlation was found between FC values of expression and vitamin D levels.

Conclusion: The present study provides further evidence for the contribution of VDR signaling and the related lncRNAs in the pathogenesis of breast cancer and introduces some novel lncRNAs as putative molecules in the interactive functional network of VDR signaling in breast cancer.