A short-term intervention with selenium affects expression of genes implicated in the epithelial-to-mesenchymal transition in the prostate

Abstract

In parallel with the inconsistency in observational studies and chemoprevention trials, the mechanisms by which selenium affects prostate cancer risk have not been elucidated. We conducted a randomized, placebo-controlled trial to examine the effects of a short-term intervention with selenium on gene expression in non-malignant prostate tissue. Twenty-three men received 300 μg selenium per day in the form of selenized yeast (n=12) or a placebo (n=11) during 5 weeks. Prostate biopsies collected from the transition zone before and after intervention were analysed for 15 participants (n=8 selenium, n=7 placebo). Pathway analyses revealed that the intervention with selenium was associated with down-regulated expression of genes involved in cellular migration, invasion, remodeling and immune responses. Specifically, expression of well-established epithelial markers, such as E-cadherin and epithelial cell adhesion molecule EPCAM, was up-regulated, while the mesenchymal markers vimentin and fibronectin were down-regulated after intervention with selenium. This implies an inhibitory effect of selenium on the epithelial-to-mesenchymal transition (EMT). Moreover, selenium was associated with down-regulated expression of genes involved in wound healing and inflammation; processes which are both related to EMT. In conclusion, our explorative data showed that selenium affected expression of genes implicated in EMT in the transition zone of the prostate.

Selenium, Selenoproteins, and Immunity

“…Other direct effects of selenium on established tumors in humans are less clear and this is particularly true for those effects that are exerted through the immune system. For example, there is some evidence from one human study suggesting an inhibitory effect of selenium on the epithelial-to-mesenchymal transition (EMT) that drives metastasis [ 157 ]. This was accompanied by the capacity of higher levels of selenium to down-regulate expression of genes involved in wound healing and inflammation, which are both related to EMT.…”

Selenium stimulates the antitumour immunity: Insights to future research

“…Furthermore, a human intervention study showed that consumption of Se-enriched foods (200 mg per serving for 3 days) increases the levels of interleukin IL-2, IL-4, IL-5, IL-13 and IL-22, indicating an activated Th 2 -type response [32]. A randomised, placebo-controlled chemoprevention trial (cohort Z 15 individuals) showed that taking selenised yeast (300 mg.day À1 ) downregulates the gene expression of tumour necrosis factor (TNF)a and transforming growth factor (TGF)b; thus, consequently inhibit the epithelial-to-mesenchymal transition (EMT) in non-malignant prostate tissue [35].…”

Emergent dynamics of underlying regulatory network links EMT and androgen receptor-dependent resistance in prostate cancer

“…To further validate our model predictions, we analyzed the following additional transcriptomic datasets – GSE77959 (human prostate specimens) (52), GSE80042 (time-course in vitro EMT induction in LNCaP cells) (45), GSE67681 (cells from mice with Pten deletion and Kras activation) (53), GSE74685 (17) (CRPC tumors) and GSE22010 (immortalized prostate epithelial cells) (55). Analysis of pairwise correlations among the ssGSEA scores for the androgen independence gene set, ZEB1 expression levels, KS and 76GS scores and ssGSEA scores for the Hallmark EMT gene set revealed positive correlations between the ssGSEA score for androgen independence and ZEB1, KS and the ssGSEA score for Hallmark EMT, and all four of these metrics correlated negatively with 76GS EMT scores (Fig 2E) .…”