Cytoplasmic NEAT1 Suppresses AML Stem Cell Self‐Renewal and Leukemogenesis through Inactivation of Wnt Signaling

Abstract As an essential component of paraspeckles, nuclear paraspeckle assembly transcript 1 (NEAT1) localizes in the nucleus, promoting progression of various malignant solid tumors. Herein, an adverse effect of NEAT1 is reported, showing that the short isoform, NEAT1_1 suppresses acute myeloid le...

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Autores principales:	Huiwen Yan, Zhi Wang, Yao Sun, Liangding Hu, Pengcheng Bu
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	acute myeloid leukemia nuclear paraspeckle assembly transcript 1 translocation ubiquitination Wnt Science Q
Acceso en línea:	https://doaj.org/article/b7f2a718550840a79ed60fdfbd44a07e
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spelling	oai:doaj.org-article:b7f2a718550840a79ed60fdfbd44a07e2021-11-17T08:40:31ZCytoplasmic NEAT1 Suppresses AML Stem Cell Self‐Renewal and Leukemogenesis through Inactivation of Wnt Signaling2198-384410.1002/advs.202100914https://doaj.org/article/b7f2a718550840a79ed60fdfbd44a07e2021-11-01T00:00:00Zhttps://doi.org/10.1002/advs.202100914https://doaj.org/toc/2198-3844Abstract As an essential component of paraspeckles, nuclear paraspeckle assembly transcript 1 (NEAT1) localizes in the nucleus, promoting progression of various malignant solid tumors. Herein, an adverse effect of NEAT1 is reported, showing that the short isoform, NEAT1_1 suppresses acute myeloid leukemia (AML) development. NEAT1_1 is downregulated in leukemia stem cells (LSCs) and its decreased expression correlates with recurrence in AML patients. It is demonstrated that NEAT1_1 suppresses leukemogenesis and LSC function but is dispensable for normal hematopoiesis. Mechanistically, NEAT1_1 is released from the nucleus into the cytoplasm of AML cells, regulated by transcription factor C/EBPβ and nuclear protein NAP1L1. Cytoplasmic NEAT1_1 interacts with Wnt component DVL2 and E3 ubiquitin ligase Trim56, facilitates Trim56‐mediated DVL2 degradation, and thus suppresses Wnt signaling. Collectively, the findings show NEAT1_1 is translocated from the nucleus to the cytoplasm and acts as a tumor suppressor in AML.Huiwen YanZhi WangYao SunLiangding HuPengcheng BuWileyarticleacute myeloid leukemianuclear paraspeckle assembly transcript 1translocationubiquitinationWntScienceQENAdvanced Science, Vol 8, Iss 22, Pp n/a-n/a (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	acute myeloid leukemia nuclear paraspeckle assembly transcript 1 translocation ubiquitination Wnt Science Q
spellingShingle	acute myeloid leukemia nuclear paraspeckle assembly transcript 1 translocation ubiquitination Wnt Science Q Huiwen Yan Zhi Wang Yao Sun Liangding Hu Pengcheng Bu Cytoplasmic NEAT1 Suppresses AML Stem Cell Self‐Renewal and Leukemogenesis through Inactivation of Wnt Signaling
description	Abstract As an essential component of paraspeckles, nuclear paraspeckle assembly transcript 1 (NEAT1) localizes in the nucleus, promoting progression of various malignant solid tumors. Herein, an adverse effect of NEAT1 is reported, showing that the short isoform, NEAT1_1 suppresses acute myeloid leukemia (AML) development. NEAT1_1 is downregulated in leukemia stem cells (LSCs) and its decreased expression correlates with recurrence in AML patients. It is demonstrated that NEAT1_1 suppresses leukemogenesis and LSC function but is dispensable for normal hematopoiesis. Mechanistically, NEAT1_1 is released from the nucleus into the cytoplasm of AML cells, regulated by transcription factor C/EBPβ and nuclear protein NAP1L1. Cytoplasmic NEAT1_1 interacts with Wnt component DVL2 and E3 ubiquitin ligase Trim56, facilitates Trim56‐mediated DVL2 degradation, and thus suppresses Wnt signaling. Collectively, the findings show NEAT1_1 is translocated from the nucleus to the cytoplasm and acts as a tumor suppressor in AML.
format	article
author	Huiwen Yan Zhi Wang Yao Sun Liangding Hu Pengcheng Bu
author_facet	Huiwen Yan Zhi Wang Yao Sun Liangding Hu Pengcheng Bu
author_sort	Huiwen Yan
title	Cytoplasmic NEAT1 Suppresses AML Stem Cell Self‐Renewal and Leukemogenesis through Inactivation of Wnt Signaling
title_short	Cytoplasmic NEAT1 Suppresses AML Stem Cell Self‐Renewal and Leukemogenesis through Inactivation of Wnt Signaling
title_full	Cytoplasmic NEAT1 Suppresses AML Stem Cell Self‐Renewal and Leukemogenesis through Inactivation of Wnt Signaling
title_fullStr	Cytoplasmic NEAT1 Suppresses AML Stem Cell Self‐Renewal and Leukemogenesis through Inactivation of Wnt Signaling
title_full_unstemmed	Cytoplasmic NEAT1 Suppresses AML Stem Cell Self‐Renewal and Leukemogenesis through Inactivation of Wnt Signaling
title_sort	cytoplasmic neat1 suppresses aml stem cell self‐renewal and leukemogenesis through inactivation of wnt signaling
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/b7f2a718550840a79ed60fdfbd44a07e
work_keys_str_mv	AT huiwenyan cytoplasmicneat1suppressesamlstemcellselfrenewalandleukemogenesisthroughinactivationofwntsignaling AT zhiwang cytoplasmicneat1suppressesamlstemcellselfrenewalandleukemogenesisthroughinactivationofwntsignaling AT yaosun cytoplasmicneat1suppressesamlstemcellselfrenewalandleukemogenesisthroughinactivationofwntsignaling AT liangdinghu cytoplasmicneat1suppressesamlstemcellselfrenewalandleukemogenesisthroughinactivationofwntsignaling AT pengchengbu cytoplasmicneat1suppressesamlstemcellselfrenewalandleukemogenesisthroughinactivationofwntsignaling
_version_	1718425693414490112

Cytoplasmic NEAT1 Suppresses AML Stem Cell Self‐Renewal and Leukemogenesis through Inactivation of Wnt Signaling

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