Suppression of Ribosome Biogenesis by Targeting WD Repeat Domain 12 (WDR12) Inhibits Glioma Stem-Like Cell Growth

Glioma stem-like cells (GSCs) are a subset of tumor cells that initiate malignant growth and promote the therapeutic resistance of glioblastoma, the most lethal primary brain tumor. Ribosome biogenesis is an essential cellular process to maintain cell growth, but its regulatory mechanism in GSCs rem...

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Autores principales:	Lanjuan Mi, Qinghui Qi, Haowen Ran, Lishu Chen, Da Li, Dake Xiao, Jiaqi Wu, Yan Cai, Songyang Zhang, Yuanyuan Li, Bohan Li, Jiong Xie, Haohao Huang, Tao Li, Tao Zhou, Ailing Li, Ji Qi, Fangye Li, Jianghong Man
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	glioblastoma (GBM) glioma stem-like cells (GSCs) WDR12 ribosome therapy of glioblastoma Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/07b9ddd034f242f78a2afe360ac3c128
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spelling	oai:doaj.org-article:07b9ddd034f242f78a2afe360ac3c1282021-11-12T07:11:01ZSuppression of Ribosome Biogenesis by Targeting WD Repeat Domain 12 (WDR12) Inhibits Glioma Stem-Like Cell Growth2234-943X10.3389/fonc.2021.751792https://doaj.org/article/07b9ddd034f242f78a2afe360ac3c1282021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.751792/fullhttps://doaj.org/toc/2234-943XGlioma stem-like cells (GSCs) are a subset of tumor cells that initiate malignant growth and promote the therapeutic resistance of glioblastoma, the most lethal primary brain tumor. Ribosome biogenesis is an essential cellular process to maintain cell growth, but its regulatory mechanism in GSCs remains largely unknown. Here, we show that WD repeat domain 12 (WDR12), a component of the Pes1-Bop1 complex (PeBoW), is required for ribosome biogenesis in GSCs. WDR12 is preferentially expressed in GSCs compared to non-stem tumor cells and normal brain cells. High levels of WDR12 are associated with glioblastoma progression and poor prognosis. Silencing WDR12 results in the degradation of PeBoW complex components and prevents the maturation of 28S rRNA, thereby inhibiting ribosome biogenesis in GSCs. Subsequently, WDR12 depletion compromises GSC proliferation, inhibits GSC-derived orthotopic tumor growth, and extends animal survival. Together, our results suggest that WDR12 is crucial for ribosome biogenesis in GSCs, and is thus a potential target for GSC-directed therapy of glioblastoma.Lanjuan MiQinghui QiHaowen RanLishu ChenDa LiDake XiaoJiaqi WuYan CaiSongyang ZhangYuanyuan LiBohan LiJiong XieHaohao HuangTao LiTao ZhouAiling LiJi QiFangye LiJianghong ManFrontiers Media S.A.articleglioblastoma (GBM)glioma stem-like cells (GSCs)WDR12ribosometherapy of glioblastomaNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	glioblastoma (GBM) glioma stem-like cells (GSCs) WDR12 ribosome therapy of glioblastoma Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	glioblastoma (GBM) glioma stem-like cells (GSCs) WDR12 ribosome therapy of glioblastoma Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Lanjuan Mi Qinghui Qi Haowen Ran Lishu Chen Da Li Dake Xiao Jiaqi Wu Yan Cai Songyang Zhang Yuanyuan Li Bohan Li Jiong Xie Haohao Huang Tao Li Tao Zhou Ailing Li Ji Qi Fangye Li Jianghong Man Suppression of Ribosome Biogenesis by Targeting WD Repeat Domain 12 (WDR12) Inhibits Glioma Stem-Like Cell Growth
description	Glioma stem-like cells (GSCs) are a subset of tumor cells that initiate malignant growth and promote the therapeutic resistance of glioblastoma, the most lethal primary brain tumor. Ribosome biogenesis is an essential cellular process to maintain cell growth, but its regulatory mechanism in GSCs remains largely unknown. Here, we show that WD repeat domain 12 (WDR12), a component of the Pes1-Bop1 complex (PeBoW), is required for ribosome biogenesis in GSCs. WDR12 is preferentially expressed in GSCs compared to non-stem tumor cells and normal brain cells. High levels of WDR12 are associated with glioblastoma progression and poor prognosis. Silencing WDR12 results in the degradation of PeBoW complex components and prevents the maturation of 28S rRNA, thereby inhibiting ribosome biogenesis in GSCs. Subsequently, WDR12 depletion compromises GSC proliferation, inhibits GSC-derived orthotopic tumor growth, and extends animal survival. Together, our results suggest that WDR12 is crucial for ribosome biogenesis in GSCs, and is thus a potential target for GSC-directed therapy of glioblastoma.
format	article
author	Lanjuan Mi Qinghui Qi Haowen Ran Lishu Chen Da Li Dake Xiao Jiaqi Wu Yan Cai Songyang Zhang Yuanyuan Li Bohan Li Jiong Xie Haohao Huang Tao Li Tao Zhou Ailing Li Ji Qi Fangye Li Jianghong Man
author_facet	Lanjuan Mi Qinghui Qi Haowen Ran Lishu Chen Da Li Dake Xiao Jiaqi Wu Yan Cai Songyang Zhang Yuanyuan Li Bohan Li Jiong Xie Haohao Huang Tao Li Tao Zhou Ailing Li Ji Qi Fangye Li Jianghong Man
author_sort	Lanjuan Mi
title	Suppression of Ribosome Biogenesis by Targeting WD Repeat Domain 12 (WDR12) Inhibits Glioma Stem-Like Cell Growth
title_short	Suppression of Ribosome Biogenesis by Targeting WD Repeat Domain 12 (WDR12) Inhibits Glioma Stem-Like Cell Growth
title_full	Suppression of Ribosome Biogenesis by Targeting WD Repeat Domain 12 (WDR12) Inhibits Glioma Stem-Like Cell Growth
title_fullStr	Suppression of Ribosome Biogenesis by Targeting WD Repeat Domain 12 (WDR12) Inhibits Glioma Stem-Like Cell Growth
title_full_unstemmed	Suppression of Ribosome Biogenesis by Targeting WD Repeat Domain 12 (WDR12) Inhibits Glioma Stem-Like Cell Growth
title_sort	suppression of ribosome biogenesis by targeting wd repeat domain 12 (wdr12) inhibits glioma stem-like cell growth
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/07b9ddd034f242f78a2afe360ac3c128
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Suppression of Ribosome Biogenesis by Targeting WD Repeat Domain 12 (WDR12) Inhibits Glioma Stem-Like Cell Growth

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