Selenoproteins of the Human Prostate: Unusual Properties and Role in Cancer Etiology

Diamond, Alan M.

doi:10.1007/s12011-019-01809-0

Cited by 19 publications

(14 citation statements)

References 79 publications

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“…Recently, Lubiński et al (2018) highlighted that in laryngeal cancer patients, the selenium level at the time of diagnosis was associated with the outcome [ 9 ]; similarly selenium supplementation in women undergoing treatment for breast cancer can favorably influence the patients’ outcomes [ 10 ]. Recently, two reviews highlighted the association between single selenoproteins and either colorectal or prostate cancer initiation and progression, as well as patient outcome, suggesting that these proteins could represent potential biomarkers or therapeutic targets [ 11 , 12 ]. Several additional reports also demonstrated the role of specific selenoproteins in other cancer types.…”

Section: Introductionmentioning

confidence: 99%

Integrated Analysis to Study the Relationship between Tumor-Associated Selenoproteins: Focus on Prostate Cancer

Capone

Polo

Sorice

et al. 2020

IJMS

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Selenoproteins are proteins that contain selenium within selenocysteine residues. To date, twenty-five mammalian selenoproteins have been identified; however, the functions of nearly half of these selenoproteins are unknown. Although alterations in selenoprotein expression and function have been suggested to play a role in cancer development and progression, few detailed studies have been carried out in this field. Network analyses and data mining of publicly available datasets on gene expression levels in different cancers, and the correlations with patient outcome, represent important tools to study the correlation between selenoproteins and other proteins present in the human interactome, and to determine whether altered selenoprotein expression is cancer type-specific, and/or correlated with cancer patient prognosis. Therefore, in the present study, we used bioinformatics approaches to (i) build up the network of interactions between twenty-five selenoproteins and identify the most inter-correlated proteins/genes, which are named HUB nodes; and (ii) analyze the correlation between selenoprotein gene expression and patient outcome in ten solid tumors. Then, considering the need to confirm by experimental approaches the correlations suggested by the bioinformatics analyses, we decided to evaluate the gene expression levels of the twenty-five selenoproteins and six HUB nodes in androgen receptor-positive (22RV1 and LNCaP) and androgen receptor–negative (DU145 and PC3) cell lines, compared to human nontransformed, and differentiated, prostate epithelial cells (EPN) by RT-qPCR analysis. This analysis confirmed that the combined evaluation of some selenoproteins and HUB nodes could have prognostic value and may improve patient outcome predictions.

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Section: Introductionmentioning

confidence: 99%

Integrated Analysis to Study the Relationship between Tumor-Associated Selenoproteins: Focus on Prostate Cancer

Capone

Polo

Sorice

et al. 2020

IJMS

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“…These data suggest that GPX1 levels will differ between individuals with the GPX1 protein with five alanines and leucine at position 198 and those with other variants. This speculation has been supported by studies examining selenium status and GPX1 genotype in the prostate [27] and plasma [97]. GPX1 variations also affect the distribution of the protein between the mitochondria and the cytoplasm, which impacts cellular energy metabolism, mitochondrial function, and expression of proteins associated with cancer progression [98,99].…”

Section: Selenium and Glutathione Peroxidase 1 Allelic Interactionsmentioning

confidence: 95%

The Interaction between Dietary Selenium Intake and Genetics in Determining Cancer Risk and Outcome

Kadkol

Diamond

2020

Nutrients

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There is considerable interest in the trace element selenium as a possible cancer chemopreventive dietary component, but supplementation trials have not indicated a clear benefit. Selenium is a critical component of selenium-containing proteins, or selenoproteins. Members of this protein family contain selenium in the form of selenocysteine. Selenocysteine is encoded by an in-frame UGA codon recognized as a selenocysteine codon by a regulatory element, the selenocysteine insertion sequence (SECIS), in the 3′-untranslated region of selenoprotein mRNAs. Epidemiological studies have implicated several selenoprotein genes in cancer risk or outcome based on associations between allelic variations and disease risk or mortality. These polymorphisms can be found in or near the SECIS or in the selenoprotein coding sequence. These variations both function to control protein synthesis and impact the efficiency of protein synthesis in response to the levels of available selenium. Thus, an individual’s genetic makeup and nutritional intake of selenium may interact to predispose them to acquiring cancer or affect cancer progression to lethality.

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“…There are only 24 and 25 selenoproteins in mice and humans, respectively. Nevertheless, selenoproteins exert a profound effect in several aspects of health, including the pathophysiology of different types of cancer [ 1 , 2 , 3 ], autoimmune diseases [ 4 ], irritable bowel syndrome [ 5 ], type 2 diabetes [ 6 , 7 ], and thyroid disorders [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Adaptive Thermogenesis in a Mouse Model Lacking Selenoprotein Biosynthesis in Brown Adipocytes

Seale

Ogawa-Wong

Watanabe

et al. 2021

IJMS

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Selenoproteins are a class of proteins with the selenium-containing amino acid selenocysteine (Sec) in their primary structure. Sec is incorporated into selenoproteins via recoding of the stop codon UGA, with specific cis and trans factors required during translation to avoid UGA recognition as a stop codon, including a Sec-specific tRNA, tRNA[Ser]Sec, encoded in mice by the gene Trsp. Whole-body deletion of Trsp in mouse is embryonically lethal, while targeted deletion of Trsp in mice has been used to understand the role of selenoproteins in the health and physiology of various tissues. We developed a mouse model with the targeted deletion of Trsp in brown adipocytes (Trspf/f-Ucp1-Cre+/−), a cell type predominant in brown adipose tissue (BAT) controlling energy expenditure via activation of adaptive thermogenesis, mostly using uncoupling protein 1 (Ucp1). At room temperature, Trspf/f-Ucp1-Cre+/− mice maintain oxygen consumption and Ucp1 expression, with male Trspf/f-Ucp1-Cre+/− mice accumulating more triglycerides in BAT than both female Trspf/f-Ucp1-Cre+/− mice or Trspf/f controls. Acute cold exposure neither reduced core body temperature nor changed the expression of selenoprotein iodothyronine deiodinase type II (Dio2), a marker of adaptive thermogenesis, in Trspf/f-Ucp1-Cre+/− mice. Microarray analysis of BAT from Trspf/f-Ucp1-Cre+/− mice revealed glutathione S-transferase alpha 3 (Gsta3) and ELMO domain containing 2 (Elmod2) as the transcripts most affected by the loss of Trsp. Male Trspf/f-Ucp1-Cre+/− mice showed mild hypothyroidism while downregulating thyroid hormone-responsive genes Thrsp and Tshr in their BATs. In summary, modest changes in the BAT of Trspf/f-Ucp1-Cre +/− mice implicate a mild thyroid hormone dysfunction in brown adipocytes.

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Selenoproteins of the Human Prostate: Unusual Properties and Role in Cancer Etiology

Cited by 19 publications

References 79 publications

Integrated Analysis to Study the Relationship between Tumor-Associated Selenoproteins: Focus on Prostate Cancer

Integrated Analysis to Study the Relationship between Tumor-Associated Selenoproteins: Focus on Prostate Cancer

The Interaction between Dietary Selenium Intake and Genetics in Determining Cancer Risk and Outcome

Adaptive Thermogenesis in a Mouse Model Lacking Selenoprotein Biosynthesis in Brown Adipocytes

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