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短期补充硒会影响前列腺中与上皮-间质转化相关基因的表达。

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

作者信息

Kok Dieuwertje E G, Kiemeney Lambertus A L M, Verhaegh Gerald W, Schalken Jack A, van Lin Emile N J T, Sedelaar J P Michiel, Witjes J Alfred, Hulsbergen-van de Kaa Christina A, van 't Veer Pieter, Kampman Ellen, Afman Lydia A

机构信息

Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.

Department for Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands.

出版信息

Oncotarget. 2017 Feb 7;8(6):10565-10579. doi: 10.18632/oncotarget.14551.

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.

摘要

与观察性研究和化学预防试验结果的不一致情况类似,硒影响前列腺癌风险的机制尚未阐明。我们开展了一项随机、安慰剂对照试验,以研究短期补充硒对非恶性前列腺组织中基因表达的影响。23名男性在5周内每天接受300微克以硒化酵母形式存在的硒(n = 12)或安慰剂(n = 11)。对15名参与者(n = 8接受硒,n = 7接受安慰剂)干预前后从移行带采集的前列腺活检组织进行了分析。通路分析显示,补充硒与细胞迁移、侵袭、重塑和免疫反应相关基因的表达下调有关。具体而言,在补充硒干预后,成熟的上皮标志物如E-钙黏蛋白和上皮细胞黏附分子EPCAM的表达上调,而间充质标志物波形蛋白和纤连蛋白的表达下调。这意味着硒对上皮-间质转化(EMT)具有抑制作用。此外,硒与伤口愈合和炎症相关基因的表达下调有关;而这两个过程均与EMT相关。总之,我们的探索性数据表明,硒影响前列腺移行带中与EMT相关的基因表达。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f9f/5354681/c8e78efb2edc/oncotarget-08-10565-g001.jpg

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