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ZNF350 promoter methylation accelerates colon cancer cell migration

Diversification of transcriptomic and epigenomic states may occur during the expansion of colorectal cancers. Certain cancer cells lose their epithelial characters and gain mesenchymal properties, known as epithelial-mesenchymal transition (EMT), and they aggressively migrate into the non-tumorigeni...

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Autores principales: Tanaka, Hiroki, Kuwano, Yuki, Nishikawa, Tatsuya, Rokutan, Kazuhito, Nishida, Kensei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6298409/
https://www.ncbi.nlm.nih.gov/pubmed/30613364
http://dx.doi.org/10.18632/oncotarget.26353
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author Tanaka, Hiroki
Kuwano, Yuki
Nishikawa, Tatsuya
Rokutan, Kazuhito
Nishida, Kensei
author_facet Tanaka, Hiroki
Kuwano, Yuki
Nishikawa, Tatsuya
Rokutan, Kazuhito
Nishida, Kensei
author_sort Tanaka, Hiroki
collection PubMed
description Diversification of transcriptomic and epigenomic states may occur during the expansion of colorectal cancers. Certain cancer cells lose their epithelial characters and gain mesenchymal properties, known as epithelial-mesenchymal transition (EMT), and they aggressively migrate into the non-tumorigenic extracellular matrix. In this study, we isolated a subpopulation with accelerated baseline motility (MG cells) and an immotile one (non-MG cells) from a colon cancer cell line (HCT116). Gene expression signatures of the MG cells indicated that this subpopulation was likely an EMT hybrid. The MG cells substantially lost their migratory properties after treatment with a methyltransferase inhibitor, 5-azacytidine, suggesting a role of DNA methylation in this process. Global transcriptome assays of both types of cells with or without 5-azacytidine treatment identified 640 genes, whose expression might be methylation-dependently down-regulated in the MG cells. Global methylation analysis revealed that 35 out of the 640 genes were hyper-methylated in the MG cells. Among them, we focused on the anti-oncogene ZNF350, which encodes a zinc-finger and BRCA1-interacting protein. Notably, ZNF350 knockdown accelerated migration of the non-MG cells, while overexpression of ZNF350 in the MG cells significantly impaired their migration. Finally, pyrosequence analysis together with dual luciferase assays of serially truncated fragments of the ZNF350 promoter (-268 to +49 bp) indicated that three hyper-methylated sites were possibly responsible for the basal promoter activity of ZNF350. Taken together, our results suggest that hyper-methylation of the ZNF350 proximal promoter may be one of the crucial determinants for acquiring increased migratory capabilities in colon cancer cells.
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spelling pubmed-62984092019-01-04 ZNF350 promoter methylation accelerates colon cancer cell migration Tanaka, Hiroki Kuwano, Yuki Nishikawa, Tatsuya Rokutan, Kazuhito Nishida, Kensei Oncotarget Research Paper Diversification of transcriptomic and epigenomic states may occur during the expansion of colorectal cancers. Certain cancer cells lose their epithelial characters and gain mesenchymal properties, known as epithelial-mesenchymal transition (EMT), and they aggressively migrate into the non-tumorigenic extracellular matrix. In this study, we isolated a subpopulation with accelerated baseline motility (MG cells) and an immotile one (non-MG cells) from a colon cancer cell line (HCT116). Gene expression signatures of the MG cells indicated that this subpopulation was likely an EMT hybrid. The MG cells substantially lost their migratory properties after treatment with a methyltransferase inhibitor, 5-azacytidine, suggesting a role of DNA methylation in this process. Global transcriptome assays of both types of cells with or without 5-azacytidine treatment identified 640 genes, whose expression might be methylation-dependently down-regulated in the MG cells. Global methylation analysis revealed that 35 out of the 640 genes were hyper-methylated in the MG cells. Among them, we focused on the anti-oncogene ZNF350, which encodes a zinc-finger and BRCA1-interacting protein. Notably, ZNF350 knockdown accelerated migration of the non-MG cells, while overexpression of ZNF350 in the MG cells significantly impaired their migration. Finally, pyrosequence analysis together with dual luciferase assays of serially truncated fragments of the ZNF350 promoter (-268 to +49 bp) indicated that three hyper-methylated sites were possibly responsible for the basal promoter activity of ZNF350. Taken together, our results suggest that hyper-methylation of the ZNF350 proximal promoter may be one of the crucial determinants for acquiring increased migratory capabilities in colon cancer cells. Impact Journals LLC 2018-12-04 /pmc/articles/PMC6298409/ /pubmed/30613364 http://dx.doi.org/10.18632/oncotarget.26353 Text en Copyright: © 2018 Tanaka 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 (http://creativecommons.org/licenses/by/3.0/) 3.0 (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
Tanaka, Hiroki
Kuwano, Yuki
Nishikawa, Tatsuya
Rokutan, Kazuhito
Nishida, Kensei
ZNF350 promoter methylation accelerates colon cancer cell migration
title ZNF350 promoter methylation accelerates colon cancer cell migration
title_full ZNF350 promoter methylation accelerates colon cancer cell migration
title_fullStr ZNF350 promoter methylation accelerates colon cancer cell migration
title_full_unstemmed ZNF350 promoter methylation accelerates colon cancer cell migration
title_short ZNF350 promoter methylation accelerates colon cancer cell migration
title_sort znf350 promoter methylation accelerates colon cancer cell migration
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6298409/
https://www.ncbi.nlm.nih.gov/pubmed/30613364
http://dx.doi.org/10.18632/oncotarget.26353
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