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Identification of downstream metastasis-associated target genes regulated by LSD1 in colon cancer cells

PURPOSE: This study aims to identify downstream target genes regulated by lysine-specific demethylase 1 (LSD1) in colon cancer cells and investigate the molecular mechanisms of LSD1 influencing invasion and metastasis of colon cancer. METHOD: We obtained the expression changes of downstream target g...

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Autores principales: Chen, Jiang, Ding, Jie, Wang, Ziwei, Zhu, Jian, Wang, Xuejian, Du, Jiyi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5386709/
https://www.ncbi.nlm.nih.gov/pubmed/28121627
http://dx.doi.org/10.18632/oncotarget.14778
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author Chen, Jiang
Ding, Jie
Wang, Ziwei
Zhu, Jian
Wang, Xuejian
Du, Jiyi
author_facet Chen, Jiang
Ding, Jie
Wang, Ziwei
Zhu, Jian
Wang, Xuejian
Du, Jiyi
author_sort Chen, Jiang
collection PubMed
description PURPOSE: This study aims to identify downstream target genes regulated by lysine-specific demethylase 1 (LSD1) in colon cancer cells and investigate the molecular mechanisms of LSD1 influencing invasion and metastasis of colon cancer. METHOD: We obtained the expression changes of downstream target genes regulated by small-interfering RNA-LSD1 and LSD1-overexpression via gene expression profiling in two human colon cancer cell lines. An Affymetrix Human Transcriptome Array 2.0 was used to identify differentially expressed genes (DEGs). We screened out LSD1-target gene associated with proliferation, metastasis, and invasion from DEGs via Gene Ontology and Pathway Studio. Subsequently, four key genes (CABYR, FOXF2, TLE4, and CDH1) were computationally predicted as metastasis-related LSD1-target genes. ChIp-PCR was applied after RT-PCR and Western blot validations to detect the occupancy of LSD1-target gene promoter-bound LSD1. RESULT: A total of 3633 DEGs were significantly upregulated, and 4642 DEGs were downregulated in LSD1-silenced SW620 cells. A total of 4047 DEGs and 4240 DEGs were upregulated and downregulated in LSD1-overexpressed HT-29 cells, respectively. RT-PCR and Western blot validated the microarray analysis results. ChIP assay results demonstrated that LSD1 might be negative regulators for target genes CABYR and CDH1. The expression level of LSD1 is negatively correlated with mono- and dimethylation of histone H3 lysine4(H3K4) at LSD1- target gene promoter region. No significant mono-methylation and dimethylation of H3 lysine9 methylation was detected at the promoter region of CABYR and CDH1. CONCLUSION: LSD1- depletion contributed to the upregulation of CABYR and CDH1 through enhancing the dimethylation of H3K4 at the LSD1-target genes promoter. LSD1- overexpression mediated the downregulation of CABYR and CDH1expression through decreasing the mono- and dimethylation of H3K4 at LSD1-target gene promoter in colon cancer cells. CABYR and CDH1 might be potential LSD1-target genes in colon carcinogenesis.
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spelling pubmed-53867092017-04-26 Identification of downstream metastasis-associated target genes regulated by LSD1 in colon cancer cells Chen, Jiang Ding, Jie Wang, Ziwei Zhu, Jian Wang, Xuejian Du, Jiyi Oncotarget Research Paper PURPOSE: This study aims to identify downstream target genes regulated by lysine-specific demethylase 1 (LSD1) in colon cancer cells and investigate the molecular mechanisms of LSD1 influencing invasion and metastasis of colon cancer. METHOD: We obtained the expression changes of downstream target genes regulated by small-interfering RNA-LSD1 and LSD1-overexpression via gene expression profiling in two human colon cancer cell lines. An Affymetrix Human Transcriptome Array 2.0 was used to identify differentially expressed genes (DEGs). We screened out LSD1-target gene associated with proliferation, metastasis, and invasion from DEGs via Gene Ontology and Pathway Studio. Subsequently, four key genes (CABYR, FOXF2, TLE4, and CDH1) were computationally predicted as metastasis-related LSD1-target genes. ChIp-PCR was applied after RT-PCR and Western blot validations to detect the occupancy of LSD1-target gene promoter-bound LSD1. RESULT: A total of 3633 DEGs were significantly upregulated, and 4642 DEGs were downregulated in LSD1-silenced SW620 cells. A total of 4047 DEGs and 4240 DEGs were upregulated and downregulated in LSD1-overexpressed HT-29 cells, respectively. RT-PCR and Western blot validated the microarray analysis results. ChIP assay results demonstrated that LSD1 might be negative regulators for target genes CABYR and CDH1. The expression level of LSD1 is negatively correlated with mono- and dimethylation of histone H3 lysine4(H3K4) at LSD1- target gene promoter region. No significant mono-methylation and dimethylation of H3 lysine9 methylation was detected at the promoter region of CABYR and CDH1. CONCLUSION: LSD1- depletion contributed to the upregulation of CABYR and CDH1 through enhancing the dimethylation of H3K4 at the LSD1-target genes promoter. LSD1- overexpression mediated the downregulation of CABYR and CDH1expression through decreasing the mono- and dimethylation of H3K4 at LSD1-target gene promoter in colon cancer cells. CABYR and CDH1 might be potential LSD1-target genes in colon carcinogenesis. Impact Journals LLC 2017-01-21 /pmc/articles/PMC5386709/ /pubmed/28121627 http://dx.doi.org/10.18632/oncotarget.14778 Text en Copyright: © 2017 Chen et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Chen, Jiang
Ding, Jie
Wang, Ziwei
Zhu, Jian
Wang, Xuejian
Du, Jiyi
Identification of downstream metastasis-associated target genes regulated by LSD1 in colon cancer cells
title Identification of downstream metastasis-associated target genes regulated by LSD1 in colon cancer cells
title_full Identification of downstream metastasis-associated target genes regulated by LSD1 in colon cancer cells
title_fullStr Identification of downstream metastasis-associated target genes regulated by LSD1 in colon cancer cells
title_full_unstemmed Identification of downstream metastasis-associated target genes regulated by LSD1 in colon cancer cells
title_short Identification of downstream metastasis-associated target genes regulated by LSD1 in colon cancer cells
title_sort identification of downstream metastasis-associated target genes regulated by lsd1 in colon cancer cells
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5386709/
https://www.ncbi.nlm.nih.gov/pubmed/28121627
http://dx.doi.org/10.18632/oncotarget.14778
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