Assessment of functional variants and expression of long noncoding RNAs in vitamin D receptor signaling in breast cancer

Abstract

PurposeVitamin D receptor (VDR) signaling pathway is implicated in the pathogenesis of breast cancer.Patients and methodsWe 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 VDR gene in all patients.ResultsVDR, MALAT1, and LINC00511 were significantly upregulated in tumoral tissues compared with ANCTs (fold change [FC] =1.85, P=0.03; FC =1.54, P=0.04; and FC =4.75, P=0.000, respectively). In patients younger than 55 years, significant associations were found between expression levels of both SNHG16 and LINC00511 genes and nuclear grade (P=0.03), expression of LINC00346 and tubule formation (P=0.01), expression of both SNHG16 and SNHG6 genes and family history of cancer (P=0.01 and 0.03, respectively), as well as expression of VDR and progesterone receptor status (P=0.03). We detected significant correlations between expression levels of VDR and SNHG16 in both tumoral tissues and ANCTs. The TT genotype of FokI polymorphism was associated with the higher expression levels of VDR. FokI variants were associated with expression levels of both MALAT1 and SNHG16 in ANCTs (P=0.01 and 0.03, respectively). CdxII variants were associated with expression levels of SNHG16 in ANCTs. A significant correlation was found between FC values of SNHG16 expression and vitamin D levels.ConclusionThe 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.

Evaluation of expression of VDR-associated lncRNAs in COVID-19 patients

“…Transcript quantities of VDR-associated genes were measured in specimens gathered from COVID-19 patients and healthy subjects using the RealQ Plus 2x Master Mix (Amplicon, Denmark). Primers Characteristics have been reported in our previous studies [ 13 , 15 ].…”

“…Moreover, expression of VDR has been shown to be affected by several mechanisms among them are long non-coding RNAs (lncRNAs) [ 12 ]. We have previously assessed expression of VDR-associated lncRNAs namely SNHG16 , SNHG6 , LINC00346 and LINC00511 in a number of disorders including epilepsy [ 13 ], lung cancer [ 14 ] and breast cancer [ 15 ]. In the current project, we have appraised expression levels of VDR , CYP27B1 and mentioned lncRNAs in the circulation of COVID-19 patients versus healthy subjects to unravel the role of these transcripts in the pathogenic processes during the course of COVID-19.…”

Vitamin D in Triple-Negative and BRCA1-Deficient Breast Cancer—Implications for Pathogenesis and Therapy

“…Some of these lncRNAs exert their effect in breast cancer through their interaction with microRNAs [99,100]. Some lncRNAs may regulate vitamin D metabolism and 1,25(OH)2D controls the expression of some miRNAs, which, in turn, regulate the mRNAs of genes involved in breast carcinogenesis [101][102][103].…”

VDR rs2228570 Polymorphism Is Related to Non-Progression to AIDS in Antiretroviral Therapy Naïve HIV-Infected Patients

“…This might be due to the three extra amino acids of the final protein, which could be disrupting a correct interaction. On the other hand, Oskooei et al [31] described that the TT genotype was associated with a higher VDR expression levels in breast cancer patients. Additionally, there are also studies that have described a lack of association between the VDR rs2228570 polymorphism and VDR expression in immune cells of European, and South African Populations [32,33], respectively.…”