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A Systematic Analysis Revealed the Potential Gene Regulatory Processes of ATRA-Triggered Neuroblastoma Differentiation and Identified a Novel RA Response Sequence in the NTRK2 Gene

文献类型：期刊论文

作者Guo, Liyuan1,2; Lin, Wei1,2; Zhang, Yidan1,2; Wang, Jing1,2
刊名BIOMED RESEARCH INTERNATIONAL
出版日期2020-02-20
卷号2020页码:19
ISSN号2314-6133
DOI10.1155/2020/6734048
通讯作者Wang, Jing(wangjing@psych.ac.cn)
英文摘要Retinoic acid- (RA-) triggered neuroblastoma cell lines are widely used cell modules of neuronal differentiation in neurodegenerative disease studies, but the gene regulatory mechanism underlying differentiation is unclear now. In this study, system biological analysis was performed on public microarray data from three neuroblastoma cell lines (SK-N-SH, SH-SY5Y-A, and SH-SY5Y-E) to explore the potential molecular processes of all-trans retinoic acid- (ATRA-) triggered differentiation. RT-qPCR, functional genomics analysis, western blotting, chromatin immunoprecipitation (ChIP), and homologous sequence analysis were further performed to validate the gene regulation processes and identify the RA response element in a specific gene. The potential disturbed biological pathways (111 functional GO terms in 14 interactive functional groups) and gene regulatory network (10 regulators and 71 regulated genes) in neuroblastoma differentiation were obtained. 15 of the 71 regulated genes are neuronal projection-related. Among them, NTRK2 is the only one that was dramatically upregulated in the RT-qPCR test that we performed on ATRA-treated SH-SY5Y-A cells. We further found that the overexpression of the NTRK2 gene can trigger differentiation-like changes in SH-SY5Y-A cells. Functional genomic analysis and western blotting assay suggested that, in neuroblastoma cells, ATRA may directly regulate the NTRK2 gene by activating the RA receptor (RAR) that binds in its promoter region. A novel RA response DNA element in the NTRK2 gene was then identified by bioinformatics analysis and chromatin immunoprecipitation (ChIP) assay. The novel element is sequence conservation and position variation among different species. Our study systematically provided the potential regulatory information of ATRA-triggered neuroblastoma differentiation, and in the NTRK2 gene, we identified a novel RA response DNA element, which may contribute to the differentiation in a human-specific manner.
WOS关键词GENOME-WIDE ANNOTATIONS ; RETINOIC ACID ; PARKINSONS-DISEASE ; NEUROTROPHIC FACTOR ; NEURONAL DIFFERENTIATION ; SYNAPTIC PLASTICITY ; SIGNALING PATHWAY ; CHRONIC STRESS ; SH-SY5Y CELLS ; EXPRESSION
资助项目National Basic Research (973) Program[2015CB351702] ; CAS Key Laboratory of Mental Health, Institute of Psychology ; CAS/SAFEA International Partnership Program for Creative Research Teams[Y2CX131003] ; Knowledge Innovation Program of the Chinese Academy of Sciences[KSCX2-EW-J-8] ; National Natural Science Foundation of China[81201046]
WOS研究方向Biotechnology & Applied Microbiology ; Research & Experimental Medicine
语种英语
WOS记录号WOS:000518931800004
出版者HINDAWI LTD
资助机构National Basic Research (973) Program ; CAS Key Laboratory of Mental Health, Institute of Psychology ; CAS/SAFEA International Partnership Program for Creative Research Teams ; Knowledge Innovation Program of the Chinese Academy of Sciences ; National Natural Science Foundation of China
源URL[http://ir.psych.ac.cn/handle/311026/31392]  
专题心理研究所_中国科学院心理健康重点实验室
通讯作者Wang, Jing
作者单位1.Chinese Acad Sci, Inst Psychol, CAS Key Lab Mental Hlth, Beijing 100101, Peoples R China
2.Univ Chinese Acad Sci, Dept Psychol, Beijing 100049, Peoples R China
推荐引用方式
GB/T 7714		 Guo, Liyuan,Lin, Wei,Zhang, Yidan,et al. A Systematic Analysis Revealed the Potential Gene Regulatory Processes of ATRA-Triggered Neuroblastoma Differentiation and Identified a Novel RA Response Sequence in the NTRK2 Gene[J]. BIOMED RESEARCH INTERNATIONAL,2020,2020:19.
APA Guo, Liyuan,Lin, Wei,Zhang, Yidan,&Wang, Jing.(2020).A Systematic Analysis Revealed the Potential Gene Regulatory Processes of ATRA-Triggered Neuroblastoma Differentiation and Identified a Novel RA Response Sequence in the NTRK2 Gene.BIOMED RESEARCH INTERNATIONAL,2020,19.
MLA Guo, Liyuan,et al."A Systematic Analysis Revealed the Potential Gene Regulatory Processes of ATRA-Triggered Neuroblastoma Differentiation and Identified a Novel RA Response Sequence in the NTRK2 Gene".BIOMED RESEARCH INTERNATIONAL 2020(2020):19.

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来源：心理研究所

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