Abstract
Prostate cancer (PCa) is one of the most common cancers in men. The main risk factors associated with the disease include older age, family history of the disease, smoking, alcohol and race. Vitamin D is a pleiotropic hormone whose low levels are associated with several diseases and a risk of cancer. Here, we undertook microarray analysis in order to identify the genes involved in PCa. We analyzed three PCa microarray datasets, overlapped all genes significantly up-regulated, and subsequently intersected the common genes identified with the down-regulated genes transcriptome of LNCaP cells treated with 1α,25(OH)2D3, in order to identify the common genes involved in PCa and potentially modulated by Vitamin D. The analysis yielded 43 genes potentially involved in PCa and significantly modulated by Vitamin D. Noteworthy, our analysis showed that six genes (PRSS8, SOX4, SMYD2, MCCC2, CCNG2 and CD2AP) were significantly modulated. A Pearson correlation analysis showed that five genes out of six (SOX4 was independent), were statistically correlated with the gene expression levels of KLK3, and with the tumor percentage. From the outcome of our investigation, it is possible to conclude that the genes identified by our analysis are associated with the PCa and are potentially modulated by the Vitamin D.
Highlights
Vitamin D is synthesized in the body through a complex series of steps beginning in the skin, under the influence of ultraviolet light, where a cholesterol precursor molecule (7-dehydrocholesterol) is transformed into the Vitamin D hormone precursor, cholecalciferol
We showed that all genes were significantly positively correlated to the tumor %
We analyzed three Prostate cancer (PCa) microarray datasets (GSE70770, GSE62872 and GSE6919), merged all the genes significantly up-regulated and subsequently, intersected the common genes identified (n = 276) with the transcriptome of genes down-regulated in the LNCaP cell line treated with Vitamin D, in order to identify the common key genes involved in PCa and potentially modulated by the action of Vitamin
Summary
Vitamin D is synthesized in the body through a complex series of steps beginning in the skin, under the influence of ultraviolet light, where a cholesterol precursor molecule (7-dehydrocholesterol) is transformed into the Vitamin D hormone precursor, cholecalciferol ( known as Vitamin D3). D3 is subsequently hydroxylated in the liver by the 25-hydroxycholecalciferol and transformed in calcidiol or calcifediol (25(OH)D3 or 25D3 ), and this latter is subjected, in the kidney, to an hydroxylation, to yield the most active hormone form of these compounds, calcitriol (1,25-dihydroxycholecalciferol or 1,25(OH) D3 or 1,25D3 ) [1]. The three main stages in Vitamin D metabolism, 25-hydroxylation, 1α-hydroxylation and 24-hydroxylation, are all performed by cytochrome P450 mixed-function oxidases (CYPs). These enzymes are distributed either in the endoplasmic reticulum (ER) (CYP2R1) or in the mitochondria (CYP27A1, CYP27B1 and CYP24A1).
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