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Genomic profiling of DVL-1 and its nuclear role as a transcriptional regulator in triple negative breast cancer

Dishevelled-1 (DVL-1) mediates Wnt signals critical for development and cellular homeostasis. DVL-1 is also linked with tumorigenesis, however its association with specific breast cancer (BC) subtypes and how it contributes to tumorigenicity remains poorly studied. Herein, using bioinformatics and g...

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Autores principales: Sharma, Monica, Castro-Piedras, Isabel, Rodgers, Austin Dwight, Pruitt, Kevin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8513712/
https://www.ncbi.nlm.nih.gov/pubmed/34659647
http://dx.doi.org/10.18632/genesandcancer.217
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author Sharma, Monica
Castro-Piedras, Isabel
Rodgers, Austin Dwight
Pruitt, Kevin
author_facet Sharma, Monica
Castro-Piedras, Isabel
Rodgers, Austin Dwight
Pruitt, Kevin
author_sort Sharma, Monica
collection PubMed
description Dishevelled-1 (DVL-1) mediates Wnt signals critical for development and cellular homeostasis. DVL-1 is also linked with tumorigenesis, however its association with specific breast cancer (BC) subtypes and how it contributes to tumorigenicity remains poorly studied. Herein, using bioinformatics and genomics analyses, we investigate the role of DVL-1 in different molecular subtypes of BC. Our results demonstrate that DVL-1 is highly expressed in triple-negative BC compared to non-cancer tissues and associated with various clinical factors that may contribute to poor prognosis and survival rate. Another critical knowledge gap which remains poorly investigated involves the role of DVL-1 in the nucleus. While the cytoplasmic role of DVL-1 as a signaling hub has been extensively studied, the nuclear role of DVL-1 remains virtually unexplored. Herein for the first time, we have performed ChIP-Seq analyses to identify genomic regions targeted and regulated by DVL-1, thus highlighting its potential role as a regulator of transcription. Furthermore, we observed that DVL-1 peaks co-localize with H3K27me3 and EZH2, a repressive epigenetic mark and a histone methyltransferase respectively. Overall, our findings emphasize the importance of DVL-1 with TNBC-related pathology and identified unexpected gene targets of DVL-1, that may help explain the complexity of aberrant Wnt signaling in cancer.
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spelling pubmed-85137122021-10-14 Genomic profiling of DVL-1 and its nuclear role as a transcriptional regulator in triple negative breast cancer Sharma, Monica Castro-Piedras, Isabel Rodgers, Austin Dwight Pruitt, Kevin Genes Cancer Research Paper Dishevelled-1 (DVL-1) mediates Wnt signals critical for development and cellular homeostasis. DVL-1 is also linked with tumorigenesis, however its association with specific breast cancer (BC) subtypes and how it contributes to tumorigenicity remains poorly studied. Herein, using bioinformatics and genomics analyses, we investigate the role of DVL-1 in different molecular subtypes of BC. Our results demonstrate that DVL-1 is highly expressed in triple-negative BC compared to non-cancer tissues and associated with various clinical factors that may contribute to poor prognosis and survival rate. Another critical knowledge gap which remains poorly investigated involves the role of DVL-1 in the nucleus. While the cytoplasmic role of DVL-1 as a signaling hub has been extensively studied, the nuclear role of DVL-1 remains virtually unexplored. Herein for the first time, we have performed ChIP-Seq analyses to identify genomic regions targeted and regulated by DVL-1, thus highlighting its potential role as a regulator of transcription. Furthermore, we observed that DVL-1 peaks co-localize with H3K27me3 and EZH2, a repressive epigenetic mark and a histone methyltransferase respectively. Overall, our findings emphasize the importance of DVL-1 with TNBC-related pathology and identified unexpected gene targets of DVL-1, that may help explain the complexity of aberrant Wnt signaling in cancer. Impact Journals LLC 2021-10-13 /pmc/articles/PMC8513712/ /pubmed/34659647 http://dx.doi.org/10.18632/genesandcancer.217 Text en https://creativecommons.org/licenses/by/3.0/Copyright: © 2021 Sharma et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Sharma, Monica
Castro-Piedras, Isabel
Rodgers, Austin Dwight
Pruitt, Kevin
Genomic profiling of DVL-1 and its nuclear role as a transcriptional regulator in triple negative breast cancer
title Genomic profiling of DVL-1 and its nuclear role as a transcriptional regulator in triple negative breast cancer
title_full Genomic profiling of DVL-1 and its nuclear role as a transcriptional regulator in triple negative breast cancer
title_fullStr Genomic profiling of DVL-1 and its nuclear role as a transcriptional regulator in triple negative breast cancer
title_full_unstemmed Genomic profiling of DVL-1 and its nuclear role as a transcriptional regulator in triple negative breast cancer
title_short Genomic profiling of DVL-1 and its nuclear role as a transcriptional regulator in triple negative breast cancer
title_sort genomic profiling of dvl-1 and its nuclear role as a transcriptional regulator in triple negative breast cancer
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8513712/
https://www.ncbi.nlm.nih.gov/pubmed/34659647
http://dx.doi.org/10.18632/genesandcancer.217
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