Decreased SATB1 expression promotes AML cell proliferation through NF-κB activation
BACKGROUND: Special AT-rich sequence-binding protein 1 (SATB1) is a chromatin-remodeling protein that regulates gene expressions in different types of cancer. Up-regulation of SATB1 is linked with progression of tumors. Our previous study showed that SATB1 expression was decreased in T cell leukemia...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6525380/ https://www.ncbi.nlm.nih.gov/pubmed/31130823 http://dx.doi.org/10.1186/s12935-019-0850-x |
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author | Luo, Xiaodan Xu, Lihua Wu, Xiaohong Tan, Huo Liu, Lian |
author_facet | Luo, Xiaodan Xu, Lihua Wu, Xiaohong Tan, Huo Liu, Lian |
author_sort | Luo, Xiaodan |
collection | PubMed |
description | BACKGROUND: Special AT-rich sequence-binding protein 1 (SATB1) is a chromatin-remodeling protein that regulates gene expressions in different types of cancer. Up-regulation of SATB1 is linked with progression of tumors. Our previous study showed that SATB1 expression was decreased in T cell leukemia/lymphoma. The contrary roles of SATB1 in solid organ tumors and hematology malignancy may provide hints to study the function of SATB1. METHODS: To characterize SATB1 mRNA and protein expression in acute myeloid leukemia (AML), we performed qRT-PCR and Western blot on bone marrow mononuclear cells from 52 newly diagnosed AML patients. Stable HL-60 cell lines with knockdown of SATB1 by shRNAs sequences (HL-60 SATB1-shRNA1 and HL-60 SATB1-shRNA2) were established. Cell proliferation, cell cycle and cell invasiveness were analyzed. Murine model was established using HL-60 SATB1-shRNAs treated nude mice and tumorigenicity was compared to study the role of SATB1 in vivo. Global gene expression profiles were analyzed in HL-60 cells with SATB1 knockdown to investigate the mechanisms underlying the regulation of AML cell growth by SATB1. RESULTS: We found that SATB1 expression was significantly decreased in patients with AML compared to normal control, and was increased after complete remission of AML. Knockdown of SATB1 enhanced the proliferation of HL-60 cells and accelerated S phase entry in vitro, and promoted the tumor growth in vivo. Global gene expression profiles were analyzed in HL-60 cells with SATB1 knockdown and the differentially expressed genes were involved in NF-κB, MAPK and PI3 K/Akt signaling pathways. Nuclear NF-κB p65 levels were significantly increased in SATB1 depleted HL-60 cells. CONCLUSIONS: Decreased SATB1 expression promotes AML cell proliferation through NF-κB activation. SATB1 could be a predictor for better response to treatment in AML. |
format | Online Article Text |
id | pubmed-6525380 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-65253802019-05-24 Decreased SATB1 expression promotes AML cell proliferation through NF-κB activation Luo, Xiaodan Xu, Lihua Wu, Xiaohong Tan, Huo Liu, Lian Cancer Cell Int Primary Research BACKGROUND: Special AT-rich sequence-binding protein 1 (SATB1) is a chromatin-remodeling protein that regulates gene expressions in different types of cancer. Up-regulation of SATB1 is linked with progression of tumors. Our previous study showed that SATB1 expression was decreased in T cell leukemia/lymphoma. The contrary roles of SATB1 in solid organ tumors and hematology malignancy may provide hints to study the function of SATB1. METHODS: To characterize SATB1 mRNA and protein expression in acute myeloid leukemia (AML), we performed qRT-PCR and Western blot on bone marrow mononuclear cells from 52 newly diagnosed AML patients. Stable HL-60 cell lines with knockdown of SATB1 by shRNAs sequences (HL-60 SATB1-shRNA1 and HL-60 SATB1-shRNA2) were established. Cell proliferation, cell cycle and cell invasiveness were analyzed. Murine model was established using HL-60 SATB1-shRNAs treated nude mice and tumorigenicity was compared to study the role of SATB1 in vivo. Global gene expression profiles were analyzed in HL-60 cells with SATB1 knockdown to investigate the mechanisms underlying the regulation of AML cell growth by SATB1. RESULTS: We found that SATB1 expression was significantly decreased in patients with AML compared to normal control, and was increased after complete remission of AML. Knockdown of SATB1 enhanced the proliferation of HL-60 cells and accelerated S phase entry in vitro, and promoted the tumor growth in vivo. Global gene expression profiles were analyzed in HL-60 cells with SATB1 knockdown and the differentially expressed genes were involved in NF-κB, MAPK and PI3 K/Akt signaling pathways. Nuclear NF-κB p65 levels were significantly increased in SATB1 depleted HL-60 cells. CONCLUSIONS: Decreased SATB1 expression promotes AML cell proliferation through NF-κB activation. SATB1 could be a predictor for better response to treatment in AML. BioMed Central 2019-05-17 /pmc/articles/PMC6525380/ /pubmed/31130823 http://dx.doi.org/10.1186/s12935-019-0850-x Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Primary Research Luo, Xiaodan Xu, Lihua Wu, Xiaohong Tan, Huo Liu, Lian Decreased SATB1 expression promotes AML cell proliferation through NF-κB activation |
title | Decreased SATB1 expression promotes AML cell proliferation through NF-κB activation |
title_full | Decreased SATB1 expression promotes AML cell proliferation through NF-κB activation |
title_fullStr | Decreased SATB1 expression promotes AML cell proliferation through NF-κB activation |
title_full_unstemmed | Decreased SATB1 expression promotes AML cell proliferation through NF-κB activation |
title_short | Decreased SATB1 expression promotes AML cell proliferation through NF-κB activation |
title_sort | decreased satb1 expression promotes aml cell proliferation through nf-κb activation |
topic | Primary Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6525380/ https://www.ncbi.nlm.nih.gov/pubmed/31130823 http://dx.doi.org/10.1186/s12935-019-0850-x |
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