TIFAB accelerates MLL-AF9−Induced acute myeloid leukemia through upregulation of HOXA9

Summary: We previously showed stabilization of NIK−induced activation of NF-κB non-canonical signaling suppresses MLL-AF9−induced AML. In the current study, we demonstrate that deletion of NF-κB non-canonical RelB prevents the inhibitory effect of NIK stabilization in MLL-AF9 AML. Mechanistically, R...

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Autores principales:	Jinming Zhao, Yan Xiu, Lin Fu, Qianze Dong, Nicholas Borcherding, Yang Wang, Qingchang Li, Nilushi S. De Silva, Ulf Klein, Brendan F. Boyce, Chen Zhao
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Biological sciences Molecular biology Cancer Science Q
Acceso en línea:	https://doaj.org/article/9c0b3adda5714869b9b0e2d2d9728712
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spelling	oai:doaj.org-article:9c0b3adda5714869b9b0e2d2d97287122021-11-26T04:37:50ZTIFAB accelerates MLL-AF9−Induced acute myeloid leukemia through upregulation of HOXA92589-004210.1016/j.isci.2021.103425https://doaj.org/article/9c0b3adda5714869b9b0e2d2d97287122021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2589004221013961https://doaj.org/toc/2589-0042Summary: We previously showed stabilization of NIK−induced activation of NF-κB non-canonical signaling suppresses MLL-AF9−induced AML. In the current study, we demonstrate that deletion of NF-κB non-canonical RelB prevents the inhibitory effect of NIK stabilization in MLL-AF9 AML. Mechanistically, RelB suppresses its direct target, TIFAB, which is upregulated in human AML and correlates negatively with the survival of AML patients. Forced expression of TIFAB reverses NIK−induced impaired AML development through downregulation of RelB and upregulation of HOXA9. Consistent with upregulation of HOXA9, gene set enrichment analysis shows that forced expression of TIFAB blocks myeloid cell development, upregulates leukemia stem cell signature and induces similar gene expression patterns to those of HOXA9-MEIS1 and HOXA9-NUP98, and upregulates oxidative phosphorylation. Accordingly, forced expression of HOXA9 also largely releases the inhibitory impact of NIK stabilization via downregulation of RelB and upregulation of RelA. Our data suggest that NIK/RelB suppresses MLL-AF9−induced AML mainly through downregulation of TIFAB/HOXA9.Jinming ZhaoYan XiuLin FuQianze DongNicholas BorcherdingYang WangQingchang LiNilushi S. De SilvaUlf KleinBrendan F. BoyceChen ZhaoElsevierarticleBiological sciencesMolecular biologyCancerScienceQENiScience, Vol 24, Iss 12, Pp 103425- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biological sciences Molecular biology Cancer Science Q
spellingShingle	Biological sciences Molecular biology Cancer Science Q Jinming Zhao Yan Xiu Lin Fu Qianze Dong Nicholas Borcherding Yang Wang Qingchang Li Nilushi S. De Silva Ulf Klein Brendan F. Boyce Chen Zhao TIFAB accelerates MLL-AF9−Induced acute myeloid leukemia through upregulation of HOXA9
description	Summary: We previously showed stabilization of NIK−induced activation of NF-κB non-canonical signaling suppresses MLL-AF9−induced AML. In the current study, we demonstrate that deletion of NF-κB non-canonical RelB prevents the inhibitory effect of NIK stabilization in MLL-AF9 AML. Mechanistically, RelB suppresses its direct target, TIFAB, which is upregulated in human AML and correlates negatively with the survival of AML patients. Forced expression of TIFAB reverses NIK−induced impaired AML development through downregulation of RelB and upregulation of HOXA9. Consistent with upregulation of HOXA9, gene set enrichment analysis shows that forced expression of TIFAB blocks myeloid cell development, upregulates leukemia stem cell signature and induces similar gene expression patterns to those of HOXA9-MEIS1 and HOXA9-NUP98, and upregulates oxidative phosphorylation. Accordingly, forced expression of HOXA9 also largely releases the inhibitory impact of NIK stabilization via downregulation of RelB and upregulation of RelA. Our data suggest that NIK/RelB suppresses MLL-AF9−induced AML mainly through downregulation of TIFAB/HOXA9.
format	article
author	Jinming Zhao Yan Xiu Lin Fu Qianze Dong Nicholas Borcherding Yang Wang Qingchang Li Nilushi S. De Silva Ulf Klein Brendan F. Boyce Chen Zhao
author_facet	Jinming Zhao Yan Xiu Lin Fu Qianze Dong Nicholas Borcherding Yang Wang Qingchang Li Nilushi S. De Silva Ulf Klein Brendan F. Boyce Chen Zhao
author_sort	Jinming Zhao
title	TIFAB accelerates MLL-AF9−Induced acute myeloid leukemia through upregulation of HOXA9
title_short	TIFAB accelerates MLL-AF9−Induced acute myeloid leukemia through upregulation of HOXA9
title_full	TIFAB accelerates MLL-AF9−Induced acute myeloid leukemia through upregulation of HOXA9
title_fullStr	TIFAB accelerates MLL-AF9−Induced acute myeloid leukemia through upregulation of HOXA9
title_full_unstemmed	TIFAB accelerates MLL-AF9−Induced acute myeloid leukemia through upregulation of HOXA9
title_sort	tifab accelerates mll-af9−induced acute myeloid leukemia through upregulation of hoxa9
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/9c0b3adda5714869b9b0e2d2d9728712
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TIFAB accelerates MLL-AF9−Induced acute myeloid leukemia through upregulation of HOXA9

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