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AURKA Suppresses Leukemic THP-1 Cell Differentiation through Inhibition of the KDM6B Pathway
Aberrations in histone modifications are being studied in mixed-lineage leukemia (MLL)-AF9-driven acute myeloid leukemia (AML). In this study, we focused on the regulation of the differentiation of the MLL-AF9 type AML cell line THP-1. We observed that, upon phorbol 12-myristate 13-acetate (PMA) tre...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Korean Society for Molecular and Cellular Biology
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5974621/ https://www.ncbi.nlm.nih.gov/pubmed/29477140 http://dx.doi.org/10.14348/molcells.2018.2311 |
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author | Park, Jin Woo Cho, Hana Oh, Hyein Kim, Ji-Young Seo, Sang-Beom |
author_facet | Park, Jin Woo Cho, Hana Oh, Hyein Kim, Ji-Young Seo, Sang-Beom |
author_sort | Park, Jin Woo |
collection | PubMed |
description | Aberrations in histone modifications are being studied in mixed-lineage leukemia (MLL)-AF9-driven acute myeloid leukemia (AML). In this study, we focused on the regulation of the differentiation of the MLL-AF9 type AML cell line THP-1. We observed that, upon phorbol 12-myristate 13-acetate (PMA) treatment, THP-1 cells differentiated into monocytes by down-regulating Aurora kinase A (AURKA), resulting in a reduction in H3S10 phosphorylation. We revealed that the AURKA inhibitor alisertib accelerates the expression of the H3K27 demethylase KDM6B, thereby dissociating AURKA and YY1 from the KDM6B promoter region. Using Flow cytometry, we found that alisertib induces THP-1 differentiation into monocytes. Furthermore, we found that treatment with the KDM6B inhibitor GSK-J4 perturbed the PMA-mediated differentiation of THP-1 cells. Thus, we discovered the mechanism of AURKA–KDM6B signaling that controls the differentiation of THP-1 cells, which has implications for biotherapy for leukemia. |
format | Online Article Text |
id | pubmed-5974621 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Korean Society for Molecular and Cellular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-59746212018-06-13 AURKA Suppresses Leukemic THP-1 Cell Differentiation through Inhibition of the KDM6B Pathway Park, Jin Woo Cho, Hana Oh, Hyein Kim, Ji-Young Seo, Sang-Beom Mol Cells Article Aberrations in histone modifications are being studied in mixed-lineage leukemia (MLL)-AF9-driven acute myeloid leukemia (AML). In this study, we focused on the regulation of the differentiation of the MLL-AF9 type AML cell line THP-1. We observed that, upon phorbol 12-myristate 13-acetate (PMA) treatment, THP-1 cells differentiated into monocytes by down-regulating Aurora kinase A (AURKA), resulting in a reduction in H3S10 phosphorylation. We revealed that the AURKA inhibitor alisertib accelerates the expression of the H3K27 demethylase KDM6B, thereby dissociating AURKA and YY1 from the KDM6B promoter region. Using Flow cytometry, we found that alisertib induces THP-1 differentiation into monocytes. Furthermore, we found that treatment with the KDM6B inhibitor GSK-J4 perturbed the PMA-mediated differentiation of THP-1 cells. Thus, we discovered the mechanism of AURKA–KDM6B signaling that controls the differentiation of THP-1 cells, which has implications for biotherapy for leukemia. Korean Society for Molecular and Cellular Biology 2018-05-31 2018-02-23 /pmc/articles/PMC5974621/ /pubmed/29477140 http://dx.doi.org/10.14348/molcells.2018.2311 Text en © The Korean Society for Molecular and Cellular Biology. All rights reserved. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/. |
spellingShingle | Article Park, Jin Woo Cho, Hana Oh, Hyein Kim, Ji-Young Seo, Sang-Beom AURKA Suppresses Leukemic THP-1 Cell Differentiation through Inhibition of the KDM6B Pathway |
title | AURKA Suppresses Leukemic THP-1 Cell Differentiation through Inhibition of the KDM6B Pathway |
title_full | AURKA Suppresses Leukemic THP-1 Cell Differentiation through Inhibition of the KDM6B Pathway |
title_fullStr | AURKA Suppresses Leukemic THP-1 Cell Differentiation through Inhibition of the KDM6B Pathway |
title_full_unstemmed | AURKA Suppresses Leukemic THP-1 Cell Differentiation through Inhibition of the KDM6B Pathway |
title_short | AURKA Suppresses Leukemic THP-1 Cell Differentiation through Inhibition of the KDM6B Pathway |
title_sort | aurka suppresses leukemic thp-1 cell differentiation through inhibition of the kdm6b pathway |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5974621/ https://www.ncbi.nlm.nih.gov/pubmed/29477140 http://dx.doi.org/10.14348/molcells.2018.2311 |
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