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Loss of SELENOF Induces the Transformed Phenotype in Human Immortalized Prostate Epithelial Cells

SELENOF is a member of the class of selenoproteins in which the amino acid selenocysteine is co-translationally inserted into the elongating peptide in response to an in-frame UGA codon located in the 3′-untranslated (3′-UTR) region of the SELENOF mRNA. Polymorphisms in the 3′-UTR are associated wit...

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Autores principales: Hong, Lenny K., Kadkol, Shrinidhi, Sverdlov, Maria, Kastrati, Irida, Elhodaky, Mostafa, Deaton, Ryan, Sfanos, Karen S., Wang, Heidi, Liu, Li, Diamond, Alan M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584825/
https://www.ncbi.nlm.nih.gov/pubmed/34769469
http://dx.doi.org/10.3390/ijms222112040
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author Hong, Lenny K.
Kadkol, Shrinidhi
Sverdlov, Maria
Kastrati, Irida
Elhodaky, Mostafa
Deaton, Ryan
Sfanos, Karen S.
Wang, Heidi
Liu, Li
Diamond, Alan M.
author_facet Hong, Lenny K.
Kadkol, Shrinidhi
Sverdlov, Maria
Kastrati, Irida
Elhodaky, Mostafa
Deaton, Ryan
Sfanos, Karen S.
Wang, Heidi
Liu, Li
Diamond, Alan M.
author_sort Hong, Lenny K.
collection PubMed
description SELENOF is a member of the class of selenoproteins in which the amino acid selenocysteine is co-translationally inserted into the elongating peptide in response to an in-frame UGA codon located in the 3′-untranslated (3′-UTR) region of the SELENOF mRNA. Polymorphisms in the 3′-UTR are associated with an increased risk of dying from prostate cancer and these variations are functional and 10 times more frequent in the genomes of African American men. SELENOF is dramatically reduced in prostate cancer compared to benign adjacent regions. Using a prostate cancer tissue microarray, it was previously established that the reduction of SELENOF in the cancers from African American men was significantly greater than in cancers from Caucasian men. When SELENOF levels in human prostate immortalized epithelial cells were reduced with an shRNA construct, those cells acquired the ability to grow in soft agar, increased the ability to migrate in a scratch assay and acquired features of energy metabolism associated with prostate cancer. These results support a role of SELENOF loss in prostate cancer progression and further indicate that SELENOF loss and genotype may contribute to the disparity in prostate cancer mortality experienced by African American men.
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spelling pubmed-85848252021-11-12 Loss of SELENOF Induces the Transformed Phenotype in Human Immortalized Prostate Epithelial Cells Hong, Lenny K. Kadkol, Shrinidhi Sverdlov, Maria Kastrati, Irida Elhodaky, Mostafa Deaton, Ryan Sfanos, Karen S. Wang, Heidi Liu, Li Diamond, Alan M. Int J Mol Sci Article SELENOF is a member of the class of selenoproteins in which the amino acid selenocysteine is co-translationally inserted into the elongating peptide in response to an in-frame UGA codon located in the 3′-untranslated (3′-UTR) region of the SELENOF mRNA. Polymorphisms in the 3′-UTR are associated with an increased risk of dying from prostate cancer and these variations are functional and 10 times more frequent in the genomes of African American men. SELENOF is dramatically reduced in prostate cancer compared to benign adjacent regions. Using a prostate cancer tissue microarray, it was previously established that the reduction of SELENOF in the cancers from African American men was significantly greater than in cancers from Caucasian men. When SELENOF levels in human prostate immortalized epithelial cells were reduced with an shRNA construct, those cells acquired the ability to grow in soft agar, increased the ability to migrate in a scratch assay and acquired features of energy metabolism associated with prostate cancer. These results support a role of SELENOF loss in prostate cancer progression and further indicate that SELENOF loss and genotype may contribute to the disparity in prostate cancer mortality experienced by African American men. MDPI 2021-11-07 /pmc/articles/PMC8584825/ /pubmed/34769469 http://dx.doi.org/10.3390/ijms222112040 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hong, Lenny K.
Kadkol, Shrinidhi
Sverdlov, Maria
Kastrati, Irida
Elhodaky, Mostafa
Deaton, Ryan
Sfanos, Karen S.
Wang, Heidi
Liu, Li
Diamond, Alan M.
Loss of SELENOF Induces the Transformed Phenotype in Human Immortalized Prostate Epithelial Cells
title Loss of SELENOF Induces the Transformed Phenotype in Human Immortalized Prostate Epithelial Cells
title_full Loss of SELENOF Induces the Transformed Phenotype in Human Immortalized Prostate Epithelial Cells
title_fullStr Loss of SELENOF Induces the Transformed Phenotype in Human Immortalized Prostate Epithelial Cells
title_full_unstemmed Loss of SELENOF Induces the Transformed Phenotype in Human Immortalized Prostate Epithelial Cells
title_short Loss of SELENOF Induces the Transformed Phenotype in Human Immortalized Prostate Epithelial Cells
title_sort loss of selenof induces the transformed phenotype in human immortalized prostate epithelial cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584825/
https://www.ncbi.nlm.nih.gov/pubmed/34769469
http://dx.doi.org/10.3390/ijms222112040
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