PTBP1 knockdown promotes neural differentiation of glioblastoma cells through UNC5B receptor

doi:10.7150/thno.71100

科研成果详情

题名	PTBP1 knockdown promotes neural differentiation of glioblastoma cells through UNC5B receptor
作者	Wang, Kankai1,2; Pan, Sishi 1,2; Zhao, Peiqi 1,2; Liu, Li 3; Chen, Zhen1,2; Bao, Han 1,2; Wang, Hao 1,2; Zhang, Ying 1,2; Zhuge, Qichuan1,2; Yang, Jianjing1,2
发表日期	2022
发表期刊	THERANOSTICS 影响因子和分区
语种	英语
原始文献类型	Article
关键词	glioblastoma cell reprogramming PTBP1 proliferation neural differentiation
其他关键词	CENTRAL-NERVOUS-SYSTEM ; PROTEIN-KINASE ; GROWTH ; RHO ; METABOLISM ; EXPRESSION ; CONVERSION ; APOPTOSIS ; DISEASE ; TUMORS
摘要	Rationale: Cell reprogramming technology is utilized to prevent cancer progression by transforming cells into terminally differentiated, non-proliferating states. Polypyrimidine tract binding protein 1 (PTBP1) is an RNA binding protein required for the growth of neurons and may directly transform multiple normal human cells into functioning neurons in vitro and in vivo when expressed at low levels. As a result, we identified it as a key to inhibiting cancer cell proliferation by boosting glioblastoma cell neural differentiation. Methods: Immunocytofluorescence (ICF) targeting TUJ1, MAP2, KI67, and EdU were utilized to evaluate glioblastoma cell reprogramming under PTBP1 knockdown or other conditions. PTBP1 and other target genes were detected using Western blotting and qRT-PCR. Activating protein phosphatase 2A (PP2A) and RhoA were detected using specific kits. CCK8 assays were employed to detect cell viability. Bioluminescence, immunohistofluorescence (IHF), and Kaplan-Meier survival analyses were utilized to demonstrate the in vivo reprogramming efficiency of PTBP1 knockdown in U87 murine glioblastoma model. In this study, RNA-seq technology was used to examine the intrinsic pathway. Results: The expression of TUJ1 and MAP2 neural markers, as well as the absence of KI67 and EdU proliferative markers in U251, U87, and KNS89 cells, indicated that glioblastoma cell reprogramming was successful. In vivo, U87 growth generated xenografts was substantially shrank due to PTBP1 knockdown induced neural differentiation, and these tumor-bearing mice had a prolonged survival time. Following RNA-seq, ten potential downstream genes were eliminated. Lentiviral interference and inhibitors blocking tests demonstrated that UNC5B receptor and its downstream signaling were essential in the neural differentiation process mediated by PTBP1 knockdown in glioblastoma cells. Conclusions: Our results indicate that PTBP1 knockdown promotes neural differentiation of glioblastoma cells via UNC5B receptor, consequently suppressing cancer cell proliferation in vitro and in vivo, providing a promising and feasible approach for glioblastoma treatment.
资助项目	National Natural Science Foundation of China [82103216, 81820108011]; Zhejiang Provincial Natural Science Foundation of China [LQ20H090005]
出版者	IVYSPRING INT PUBL
出版地	LAKE HAVEN
ISSN	1838-7640
卷号	12 期号:8 页码:3847-3861
DOI	10.7150/thno.71100
页数	15
WOS类目	Medicine, Research & Experimental
WOS研究方向	Research & Experimental Medicine
WOS记录号	WOS:000803991200004
收录类别	SCIE ; SCOPUS ; PUBMED
URL	查看原文
Pubmed记录号	35664063
Scopus记录号	2-s2.0-85131341987
通讯作者地址	[Zhuge, Qichuan]Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research,The First Affiliated Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,325000,China ; [Yang, Jianjing]Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research,The First Affiliated Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,325000,China
scopus学科分类	Medicine (miscellaneous);Pharmacology, Toxicology and Pharmaceutics (miscellaneous)
引用统计	被引频次[WOS]：0 [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/148340
专题	第一临床医学院（信息与工程学院）、附属第一医院_老化与神经疾病重点实验室附属第一医院_神经外科
通讯作者	Zhuge, Qichuan; Yang, Jianjing
作者单位	1.Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325000,China; 2.Department of Neurosurgery,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325000,China; 3.Zhejiang Provincial Key Laboratory of Interventional Pulmonology,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325000,China
第一作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院
通讯作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院
第一作者的第一单位	附属第一医院
推荐引用方式 GB/T 7714	Wang, Kankai,Pan, Sishi,Zhao, Peiqi,et al. PTBP1 knockdown promotes neural differentiation of glioblastoma cells through UNC5B receptor[J]. THERANOSTICS,2022,12(8):3847-3861.
APA	Wang, Kankai., Pan, Sishi., Zhao, Peiqi., Liu, Li., Chen, Zhen., ... & Yang, Jianjing. (2022). PTBP1 knockdown promotes neural differentiation of glioblastoma cells through UNC5B receptor. THERANOSTICS, 12(8), 3847-3861.
MLA	Wang, Kankai,et al."PTBP1 knockdown promotes neural differentiation of glioblastoma cells through UNC5B receptor".THERANOSTICS 12.8(2022):3847-3861.