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Effects on prostate cancer cells of targeting RNA polymerase III
RNA polymerase (pol) III occurs in two forms, containing either the POLR3G subunit or the related paralogue POLR3GL. Whereas POLR3GL is ubiquitous, POLR3G is enriched in undifferentiated cells. Depletion of POLR3G selectively triggers proliferative arrest and differentiation of prostate cancer cells...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6486637/ https://www.ncbi.nlm.nih.gov/pubmed/30820548 http://dx.doi.org/10.1093/nar/gkz128 |
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author | Petrie, John L Swan, Caroline Ingram, Richard M Frame, Fiona M Collins, Anne T Dumay-Odelot, Hélène Teichmann, Martin Maitland, Norman J White, Robert J |
author_facet | Petrie, John L Swan, Caroline Ingram, Richard M Frame, Fiona M Collins, Anne T Dumay-Odelot, Hélène Teichmann, Martin Maitland, Norman J White, Robert J |
author_sort | Petrie, John L |
collection | PubMed |
description | RNA polymerase (pol) III occurs in two forms, containing either the POLR3G subunit or the related paralogue POLR3GL. Whereas POLR3GL is ubiquitous, POLR3G is enriched in undifferentiated cells. Depletion of POLR3G selectively triggers proliferative arrest and differentiation of prostate cancer cells, responses not elicited when POLR3GL is depleted. A small molecule pol III inhibitor can cause POLR3G depletion, induce similar differentiation and suppress proliferation and viability of cancer cells. This response involves control of the fate-determining factor NANOG by small RNAs derived from Alu short interspersed nuclear elements. Tumour initiating activity in vivo can be reduced by transient exposure to the pol III inhibitor. Untransformed prostate cells appear less sensitive than cancer cells to pol III depletion or inhibition, raising the possibility of a therapeutic window. |
format | Online Article Text |
id | pubmed-6486637 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-64866372019-05-01 Effects on prostate cancer cells of targeting RNA polymerase III Petrie, John L Swan, Caroline Ingram, Richard M Frame, Fiona M Collins, Anne T Dumay-Odelot, Hélène Teichmann, Martin Maitland, Norman J White, Robert J Nucleic Acids Res Gene regulation, Chromatin and Epigenetics RNA polymerase (pol) III occurs in two forms, containing either the POLR3G subunit or the related paralogue POLR3GL. Whereas POLR3GL is ubiquitous, POLR3G is enriched in undifferentiated cells. Depletion of POLR3G selectively triggers proliferative arrest and differentiation of prostate cancer cells, responses not elicited when POLR3GL is depleted. A small molecule pol III inhibitor can cause POLR3G depletion, induce similar differentiation and suppress proliferation and viability of cancer cells. This response involves control of the fate-determining factor NANOG by small RNAs derived from Alu short interspersed nuclear elements. Tumour initiating activity in vivo can be reduced by transient exposure to the pol III inhibitor. Untransformed prostate cells appear less sensitive than cancer cells to pol III depletion or inhibition, raising the possibility of a therapeutic window. Oxford University Press 2019-05-07 2019-03-01 /pmc/articles/PMC6486637/ /pubmed/30820548 http://dx.doi.org/10.1093/nar/gkz128 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Gene regulation, Chromatin and Epigenetics Petrie, John L Swan, Caroline Ingram, Richard M Frame, Fiona M Collins, Anne T Dumay-Odelot, Hélène Teichmann, Martin Maitland, Norman J White, Robert J Effects on prostate cancer cells of targeting RNA polymerase III |
title | Effects on prostate cancer cells of targeting RNA polymerase III |
title_full | Effects on prostate cancer cells of targeting RNA polymerase III |
title_fullStr | Effects on prostate cancer cells of targeting RNA polymerase III |
title_full_unstemmed | Effects on prostate cancer cells of targeting RNA polymerase III |
title_short | Effects on prostate cancer cells of targeting RNA polymerase III |
title_sort | effects on prostate cancer cells of targeting rna polymerase iii |
topic | Gene regulation, Chromatin and Epigenetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6486637/ https://www.ncbi.nlm.nih.gov/pubmed/30820548 http://dx.doi.org/10.1093/nar/gkz128 |
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