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Genomic Amplification and Functional Dependency of the Gamma Actin Gene ACTG1 in Uterine Cancer

Sarcomere and cytoskeleton genes, or actomyosin genes, regulate cell biology including mechanical stress, cell motility, and cell division. While actomyosin genes are recurrently dysregulated in cancers, their oncogenic roles have not been examined in a lineage-specific fashion. In this report, we i...

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Autores principales: Richter, Camden, Mayhew, David, Rennhack, Jonathan P., So, Jonathan, Stover, Elizabeth H., Hwang, Justin H., Szczesna-Cordary, Danuta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698702/
https://www.ncbi.nlm.nih.gov/pubmed/33217970
http://dx.doi.org/10.3390/ijms21228690
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author Richter, Camden
Mayhew, David
Rennhack, Jonathan P.
So, Jonathan
Stover, Elizabeth H.
Hwang, Justin H.
Szczesna-Cordary, Danuta
author_facet Richter, Camden
Mayhew, David
Rennhack, Jonathan P.
So, Jonathan
Stover, Elizabeth H.
Hwang, Justin H.
Szczesna-Cordary, Danuta
author_sort Richter, Camden
collection PubMed
description Sarcomere and cytoskeleton genes, or actomyosin genes, regulate cell biology including mechanical stress, cell motility, and cell division. While actomyosin genes are recurrently dysregulated in cancers, their oncogenic roles have not been examined in a lineage-specific fashion. In this report, we investigated dysregulation of nine sarcomeric and cytoskeletal genes across 20 cancer lineages. We found that uterine cancers harbored the highest frequencies of amplification and overexpression of the gamma actin gene, ACTG1. Each of the four subtypes of uterine cancers, mixed endometrial carcinomas, serous carcinomas, endometroid carcinomas, and carcinosarcomas harbored between 5~20% of ACTG1 gene amplification or overexpression. Clinically, patients with ACTG1 gains had a poor prognosis. ACTG1 gains showed transcriptional patterns that reflect activation of oncogenic signals, repressed response to innate immunity, or immunotherapy. Functionally, the CRISPR-CAS9 gene deletion of ACTG1 had the most robust and consistent effects in uterine cancer cells relative to 20 other lineages. Overall, we propose that ACTG1 regulates the fitness of uterine cancer cells by modulating cell-intrinsic properties and the tumor microenvironment. In summary, the ACTG1 functions relative to other actomyosin genes support the notion that it is a potential biomarker and a target gene in uterine cancer precision therapies.
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spelling pubmed-76987022020-11-29 Genomic Amplification and Functional Dependency of the Gamma Actin Gene ACTG1 in Uterine Cancer Richter, Camden Mayhew, David Rennhack, Jonathan P. So, Jonathan Stover, Elizabeth H. Hwang, Justin H. Szczesna-Cordary, Danuta Int J Mol Sci Article Sarcomere and cytoskeleton genes, or actomyosin genes, regulate cell biology including mechanical stress, cell motility, and cell division. While actomyosin genes are recurrently dysregulated in cancers, their oncogenic roles have not been examined in a lineage-specific fashion. In this report, we investigated dysregulation of nine sarcomeric and cytoskeletal genes across 20 cancer lineages. We found that uterine cancers harbored the highest frequencies of amplification and overexpression of the gamma actin gene, ACTG1. Each of the four subtypes of uterine cancers, mixed endometrial carcinomas, serous carcinomas, endometroid carcinomas, and carcinosarcomas harbored between 5~20% of ACTG1 gene amplification or overexpression. Clinically, patients with ACTG1 gains had a poor prognosis. ACTG1 gains showed transcriptional patterns that reflect activation of oncogenic signals, repressed response to innate immunity, or immunotherapy. Functionally, the CRISPR-CAS9 gene deletion of ACTG1 had the most robust and consistent effects in uterine cancer cells relative to 20 other lineages. Overall, we propose that ACTG1 regulates the fitness of uterine cancer cells by modulating cell-intrinsic properties and the tumor microenvironment. In summary, the ACTG1 functions relative to other actomyosin genes support the notion that it is a potential biomarker and a target gene in uterine cancer precision therapies. MDPI 2020-11-18 /pmc/articles/PMC7698702/ /pubmed/33217970 http://dx.doi.org/10.3390/ijms21228690 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Richter, Camden
Mayhew, David
Rennhack, Jonathan P.
So, Jonathan
Stover, Elizabeth H.
Hwang, Justin H.
Szczesna-Cordary, Danuta
Genomic Amplification and Functional Dependency of the Gamma Actin Gene ACTG1 in Uterine Cancer
title Genomic Amplification and Functional Dependency of the Gamma Actin Gene ACTG1 in Uterine Cancer
title_full Genomic Amplification and Functional Dependency of the Gamma Actin Gene ACTG1 in Uterine Cancer
title_fullStr Genomic Amplification and Functional Dependency of the Gamma Actin Gene ACTG1 in Uterine Cancer
title_full_unstemmed Genomic Amplification and Functional Dependency of the Gamma Actin Gene ACTG1 in Uterine Cancer
title_short Genomic Amplification and Functional Dependency of the Gamma Actin Gene ACTG1 in Uterine Cancer
title_sort genomic amplification and functional dependency of the gamma actin gene actg1 in uterine cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698702/
https://www.ncbi.nlm.nih.gov/pubmed/33217970
http://dx.doi.org/10.3390/ijms21228690
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