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MOZ Forms an Autoregulatory Feedback Loop with miR-223 in AML and Monocyte/Macrophage Development
Monocytic leukemia zinc-finger protein (MOZ) has been found to form fusion proteins with many regulators in acute myeloid leukemia (AML). However, the molecular functions and underlying mechanism of MOZ in AML is not well understood. Here, clinical MOZ expression analysis combined with data integrat...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321978/ https://www.ncbi.nlm.nih.gov/pubmed/30616103 http://dx.doi.org/10.1016/j.isci.2018.12.016 |
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author | Jiang, Ming Zhang, Ju Qian, Lili Miao, Yuhui Song, Weiguo Liu, Hanyuan Li, Rui |
author_facet | Jiang, Ming Zhang, Ju Qian, Lili Miao, Yuhui Song, Weiguo Liu, Hanyuan Li, Rui |
author_sort | Jiang, Ming |
collection | PubMed |
description | Monocytic leukemia zinc-finger protein (MOZ) has been found to form fusion proteins with many regulators in acute myeloid leukemia (AML). However, the molecular functions and underlying mechanism of MOZ in AML is not well understood. Here, clinical MOZ expression analysis combined with data integration from the TCGA and GEO databases indicated that a low level of MOZ was associated with poor prognosis. MOZ knockdown inhibited monocyte differentiation and increased resistance to chemotherapeutic drug-induced apoptosis in THP-1 or U937 cells. In addition, we found that genetic silencing of MOZ suppressed AP-1 and AKT activity in the context of lipopolysaccharide stimulation, resulting in diminished M1 activation of macrophages. We further showed that MOZ was a validated target of miR-223 and functioned as a repressor of miR-223 expression. Our study indicates that a molecular network involving MOZ and miR-223 contributes to the monocyte differentiation and polarization program, which is deregulated in AML. |
format | Online Article Text |
id | pubmed-6321978 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-63219782019-01-09 MOZ Forms an Autoregulatory Feedback Loop with miR-223 in AML and Monocyte/Macrophage Development Jiang, Ming Zhang, Ju Qian, Lili Miao, Yuhui Song, Weiguo Liu, Hanyuan Li, Rui iScience Article Monocytic leukemia zinc-finger protein (MOZ) has been found to form fusion proteins with many regulators in acute myeloid leukemia (AML). However, the molecular functions and underlying mechanism of MOZ in AML is not well understood. Here, clinical MOZ expression analysis combined with data integration from the TCGA and GEO databases indicated that a low level of MOZ was associated with poor prognosis. MOZ knockdown inhibited monocyte differentiation and increased resistance to chemotherapeutic drug-induced apoptosis in THP-1 or U937 cells. In addition, we found that genetic silencing of MOZ suppressed AP-1 and AKT activity in the context of lipopolysaccharide stimulation, resulting in diminished M1 activation of macrophages. We further showed that MOZ was a validated target of miR-223 and functioned as a repressor of miR-223 expression. Our study indicates that a molecular network involving MOZ and miR-223 contributes to the monocyte differentiation and polarization program, which is deregulated in AML. Elsevier 2018-12-21 /pmc/articles/PMC6321978/ /pubmed/30616103 http://dx.doi.org/10.1016/j.isci.2018.12.016 Text en © 2018 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Jiang, Ming Zhang, Ju Qian, Lili Miao, Yuhui Song, Weiguo Liu, Hanyuan Li, Rui MOZ Forms an Autoregulatory Feedback Loop with miR-223 in AML and Monocyte/Macrophage Development |
title | MOZ Forms an Autoregulatory Feedback Loop with miR-223 in AML and Monocyte/Macrophage Development |
title_full | MOZ Forms an Autoregulatory Feedback Loop with miR-223 in AML and Monocyte/Macrophage Development |
title_fullStr | MOZ Forms an Autoregulatory Feedback Loop with miR-223 in AML and Monocyte/Macrophage Development |
title_full_unstemmed | MOZ Forms an Autoregulatory Feedback Loop with miR-223 in AML and Monocyte/Macrophage Development |
title_short | MOZ Forms an Autoregulatory Feedback Loop with miR-223 in AML and Monocyte/Macrophage Development |
title_sort | moz forms an autoregulatory feedback loop with mir-223 in aml and monocyte/macrophage development |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321978/ https://www.ncbi.nlm.nih.gov/pubmed/30616103 http://dx.doi.org/10.1016/j.isci.2018.12.016 |
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