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TIFAB通过上调HOXA9促进MLL-AF9诱导的急性髓系白血病。

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

作者信息

Zhao Jinming, Xiu Yan, Fu Lin, Dong Qianze, Borcherding Nicholas, Wang Yang, Li Qingchang, De Silva Nilushi S, Klein Ulf, Boyce Brendan F, Zhao Chen

机构信息

Department of Pathology, Case Western Reserve University, Wolstein Research Building, Room 6503 2103 Cornell Road, Cleveland, OH 44106, USA.

Department of Pathology, China Medical University, 77 Puhe Road, Shenbei Xinqu, Shenyang, Liaoning Province, 110122, China.

出版信息

iScience. 2021 Nov 12;24(12):103425. doi: 10.1016/j.isci.2021.103425. eCollection 2021 Dec 17.

DOI:10.1016/j.isci.2021.103425
PMID:34877491
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8633042/
Abstract

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.

摘要

我们之前表明，NIK诱导的NF-κB非经典信号激活的稳定化可抑制MLL-AF9诱导的急性髓系白血病（AML）。在当前研究中，我们证明NF-κB非经典RelB的缺失可消除NIK稳定化在MLL-AF9 AML中的抑制作用。从机制上讲，RelB抑制其直接靶点TIFAB，TIFAB在人类AML中上调，且与AML患者的生存率呈负相关。TIFAB的强制表达通过下调RelB和上调HOXA9来逆转NIK诱导的AML发育受损。与HOXA9的上调一致，基因集富集分析表明，TIFAB的强制表达可阻断髓系细胞发育，上调白血病干细胞特征，并诱导出与HOXA9-MEIS1和HOXA9-NUP98相似的基因表达模式，还上调氧化磷酸化。因此，HOXA9的强制表达也主要通过下调RelB和上调RelA来很大程度上解除NIK稳定化的抑制作用。我们的数据表明，NIK/RelB主要通过下调TIFAB/HOXA9来抑制MLL-AF9诱导的AML。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a3c/8633042/68c5bec36c29/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a3c/8633042/561a96cecaa9/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a3c/8633042/164e9476def8/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a3c/8633042/c4277fa42d7c/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a3c/8633042/bb3548256ab4/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a3c/8633042/68c5bec36c29/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a3c/8633042/561a96cecaa9/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a3c/8633042/164e9476def8/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a3c/8633042/c4277fa42d7c/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a3c/8633042/bb3548256ab4/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a3c/8633042/68c5bec36c29/gr4.jpg

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本文引用的文献

1
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Front Oncol. 2020 Dec 23;10:612880. doi: 10.3389/fonc.2020.612880. eCollection 2020.
2
HOX genes and the NF-κB pathway: A convergence of developmental biology, inflammation and cancer biology.HOX 基因与 NF-κB 通路：发育生物学、炎症和癌症生物学的交汇点。
Biochim Biophys Acta Rev Cancer. 2020 Dec;1874(2):188450. doi: 10.1016/j.bbcan.2020.188450. Epub 2020 Oct 10.
3
TIFA and TIFAB: FHA-domain proteins involved in inflammation, hematopoiesis, and disease.
核因子-κB：急性髓系白血病中的一个可药物作用靶点。
Cancers (Basel). 2022 Jul 21;14(14):3557. doi: 10.3390/cancers14143557.
TIFA 和 TIFAB：参与炎症、造血和疾病的 FHA 结构域蛋白。
Exp Hematol. 2020 Oct;90:18-29. doi: 10.1016/j.exphem.2020.08.010. Epub 2020 Sep 7.
4
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Nat Immunol. 2020 May;21(5):535-545. doi: 10.1038/s41590-020-0663-z. Epub 2020 Apr 20.
5
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6
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8
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