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Fatty acid synthase reprograms the epigenome in uterine leiomyosarcomas
SK-UT-1 uterine leiomyosarcomas (Ut-LMS) cells were transduced with a fatty acid synthase (FASN)-containing retroviral vector to recapitulate the “lipogenic phenotype of cancer.” Consistent with this model, forced expression of FASN enhanced SK-UT-1 proliferation, migration, and cellular motion. Fur...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5487038/ https://www.ncbi.nlm.nih.gov/pubmed/28654693 http://dx.doi.org/10.1371/journal.pone.0179692 |
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author | Guan, Min Wu, Xiwei Chu, Peiguo Chow, Warren A. |
author_facet | Guan, Min Wu, Xiwei Chu, Peiguo Chow, Warren A. |
author_sort | Guan, Min |
collection | PubMed |
description | SK-UT-1 uterine leiomyosarcomas (Ut-LMS) cells were transduced with a fatty acid synthase (FASN)-containing retroviral vector to recapitulate the “lipogenic phenotype of cancer.” Consistent with this model, forced expression of FASN enhanced SK-UT-1 proliferation, migration, and cellular motion. Further investigation showed FASN promotes trimethylation of H3K9 (H3K9me3) and acetylation of H3K27 (H3K27ac) in SK-UT-1 cells. In contrast, siRNA targeting of FASN in high endogenous FASN expressing SK-LMS-1 Ut-LMS cells inhibits trimethylation of H3K9 and acetylation of H3K27. Palmitate, the predominant fatty acid product of FASN, increased H3K9me3, H3K27ac and H3K27me3 detection in SK-UT-1 cells. FASN promoted histone 3 methylation and acetylation through alteration of histone 3-modifying enzymatic activities (HDAC, HDM, HMT and HAT). ChIP-seq in SK-UT-1-FASN cells with anti-H3K9me3 antibody identified regions of enriched binding compared to vector-only cells. One differentially-enriched gene, CRISP1, was investigated further by ChIP-PCR. The transcriptionally repressive function of H3K9me3 was confirmed in CRISP1. Our results provide mechanistic insight into the pathobiology of the “lipogenic phenotype of cancer.” Here, FASN reprograms the Ut-LMS epigenome through chromatin remodeling to promote the “malignant phenotype.” |
format | Online Article Text |
id | pubmed-5487038 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-54870382017-07-11 Fatty acid synthase reprograms the epigenome in uterine leiomyosarcomas Guan, Min Wu, Xiwei Chu, Peiguo Chow, Warren A. PLoS One Research Article SK-UT-1 uterine leiomyosarcomas (Ut-LMS) cells were transduced with a fatty acid synthase (FASN)-containing retroviral vector to recapitulate the “lipogenic phenotype of cancer.” Consistent with this model, forced expression of FASN enhanced SK-UT-1 proliferation, migration, and cellular motion. Further investigation showed FASN promotes trimethylation of H3K9 (H3K9me3) and acetylation of H3K27 (H3K27ac) in SK-UT-1 cells. In contrast, siRNA targeting of FASN in high endogenous FASN expressing SK-LMS-1 Ut-LMS cells inhibits trimethylation of H3K9 and acetylation of H3K27. Palmitate, the predominant fatty acid product of FASN, increased H3K9me3, H3K27ac and H3K27me3 detection in SK-UT-1 cells. FASN promoted histone 3 methylation and acetylation through alteration of histone 3-modifying enzymatic activities (HDAC, HDM, HMT and HAT). ChIP-seq in SK-UT-1-FASN cells with anti-H3K9me3 antibody identified regions of enriched binding compared to vector-only cells. One differentially-enriched gene, CRISP1, was investigated further by ChIP-PCR. The transcriptionally repressive function of H3K9me3 was confirmed in CRISP1. Our results provide mechanistic insight into the pathobiology of the “lipogenic phenotype of cancer.” Here, FASN reprograms the Ut-LMS epigenome through chromatin remodeling to promote the “malignant phenotype.” Public Library of Science 2017-06-27 /pmc/articles/PMC5487038/ /pubmed/28654693 http://dx.doi.org/10.1371/journal.pone.0179692 Text en © 2017 Guan et al 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 use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Guan, Min Wu, Xiwei Chu, Peiguo Chow, Warren A. Fatty acid synthase reprograms the epigenome in uterine leiomyosarcomas |
title | Fatty acid synthase reprograms the epigenome in uterine leiomyosarcomas |
title_full | Fatty acid synthase reprograms the epigenome in uterine leiomyosarcomas |
title_fullStr | Fatty acid synthase reprograms the epigenome in uterine leiomyosarcomas |
title_full_unstemmed | Fatty acid synthase reprograms the epigenome in uterine leiomyosarcomas |
title_short | Fatty acid synthase reprograms the epigenome in uterine leiomyosarcomas |
title_sort | fatty acid synthase reprograms the epigenome in uterine leiomyosarcomas |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5487038/ https://www.ncbi.nlm.nih.gov/pubmed/28654693 http://dx.doi.org/10.1371/journal.pone.0179692 |
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