Pseudogene RPL32P3 regulates the blood–tumor barrier permeability via the YBX2/HNF4G axis

Abstract The existence of the blood–tumor barrier (BTB) severely hinders the transport of anti-tumor drugs to brain tumor tissues. Selectively opening BTB is of great significance to improve the chemotherapy effect of glioma. Pseudogenes have been recognized as important regulators in various biolog...

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Autores principales:	Ye Ding, Xiaobai Liu, Chunqing Yang, Xuelei Ruan, Di Wang, Yunhui Liu, Xiuli Shang, Qianshuo Liu, Shuyuan Shen, Lu Zhu, Yixue Xue
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671
Acceso en línea:	https://doaj.org/article/98bcc4f27b43410c934c02a39b0925b3
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spelling	oai:doaj.org-article:98bcc4f27b43410c934c02a39b0925b32021-11-28T12:10:35ZPseudogene RPL32P3 regulates the blood–tumor barrier permeability via the YBX2/HNF4G axis10.1038/s41420-021-00758-92058-7716https://doaj.org/article/98bcc4f27b43410c934c02a39b0925b32021-11-01T00:00:00Zhttps://doi.org/10.1038/s41420-021-00758-9https://doaj.org/toc/2058-7716Abstract The existence of the blood–tumor barrier (BTB) severely hinders the transport of anti-tumor drugs to brain tumor tissues. Selectively opening BTB is of great significance to improve the chemotherapy effect of glioma. Pseudogenes have been recognized as important regulators in various biologic processes. In this study, we identified that ribosomal protein L32 pseudogene 3 (RPL32P3) was highly expressed in glioma-exposed endothelial cells (GECs). Knockdown of RPL32P3 decreased the expression of tight junction-related proteins (TJPs) and increased BTB permeability. Subsequent analysis of the underlying mechanism indicated that RPL32P3 recruited lysine methyltransferase 2 A (KMT2A) to the Y-box binding protein 2 (YBX2) promoter region and mediated H3K4me3 to promote YBX2 transcription. Highly expressed YBX2 bound and stabilized hepatocyte nuclear factor 4 gamma (HNF4G) mRNA. Highly expressed HNF4G directly bound to the promoters of TJPs ZO-1, occludin and claudin-5 to promote their transcriptional activities and regulated BTB permeability. The simultaneous knockdown of RPL32P3, YBX2, and HNF4G combined with doxorubicin (DOX) increased the apoptosis of glioma cells. In conclusion, the current study indicated that RPL32P3 knockdown increased BTB permeability through the YBX2/HNF4G pathway. These findings may provide new targets for the comprehensive treatment of glioma.Ye DingXiaobai LiuChunqing YangXuelei RuanDi WangYunhui LiuXiuli ShangQianshuo LiuShuyuan ShenLu ZhuYixue XueNature Publishing GrouparticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282CytologyQH573-671ENCell Death Discovery, Vol 7, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671 Ye Ding Xiaobai Liu Chunqing Yang Xuelei Ruan Di Wang Yunhui Liu Xiuli Shang Qianshuo Liu Shuyuan Shen Lu Zhu Yixue Xue Pseudogene RPL32P3 regulates the blood–tumor barrier permeability via the YBX2/HNF4G axis
description	Abstract The existence of the blood–tumor barrier (BTB) severely hinders the transport of anti-tumor drugs to brain tumor tissues. Selectively opening BTB is of great significance to improve the chemotherapy effect of glioma. Pseudogenes have been recognized as important regulators in various biologic processes. In this study, we identified that ribosomal protein L32 pseudogene 3 (RPL32P3) was highly expressed in glioma-exposed endothelial cells (GECs). Knockdown of RPL32P3 decreased the expression of tight junction-related proteins (TJPs) and increased BTB permeability. Subsequent analysis of the underlying mechanism indicated that RPL32P3 recruited lysine methyltransferase 2 A (KMT2A) to the Y-box binding protein 2 (YBX2) promoter region and mediated H3K4me3 to promote YBX2 transcription. Highly expressed YBX2 bound and stabilized hepatocyte nuclear factor 4 gamma (HNF4G) mRNA. Highly expressed HNF4G directly bound to the promoters of TJPs ZO-1, occludin and claudin-5 to promote their transcriptional activities and regulated BTB permeability. The simultaneous knockdown of RPL32P3, YBX2, and HNF4G combined with doxorubicin (DOX) increased the apoptosis of glioma cells. In conclusion, the current study indicated that RPL32P3 knockdown increased BTB permeability through the YBX2/HNF4G pathway. These findings may provide new targets for the comprehensive treatment of glioma.
format	article
author	Ye Ding Xiaobai Liu Chunqing Yang Xuelei Ruan Di Wang Yunhui Liu Xiuli Shang Qianshuo Liu Shuyuan Shen Lu Zhu Yixue Xue
author_facet	Ye Ding Xiaobai Liu Chunqing Yang Xuelei Ruan Di Wang Yunhui Liu Xiuli Shang Qianshuo Liu Shuyuan Shen Lu Zhu Yixue Xue
author_sort	Ye Ding
title	Pseudogene RPL32P3 regulates the blood–tumor barrier permeability via the YBX2/HNF4G axis
title_short	Pseudogene RPL32P3 regulates the blood–tumor barrier permeability via the YBX2/HNF4G axis
title_full	Pseudogene RPL32P3 regulates the blood–tumor barrier permeability via the YBX2/HNF4G axis
title_fullStr	Pseudogene RPL32P3 regulates the blood–tumor barrier permeability via the YBX2/HNF4G axis
title_full_unstemmed	Pseudogene RPL32P3 regulates the blood–tumor barrier permeability via the YBX2/HNF4G axis
title_sort	pseudogene rpl32p3 regulates the blood–tumor barrier permeability via the ybx2/hnf4g axis
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/98bcc4f27b43410c934c02a39b0925b3
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Pseudogene RPL32P3 regulates the blood–tumor barrier permeability via the YBX2/HNF4G axis

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