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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
Guo, Liyuan1,2; Lin, Wei1,2; Zhang, Yidan1,2; Wang, Jing1,2
First AuthorGuo, Liyuan
Correspondent Emailwangjing@psych.ac.cn
Contribution Rank1
Abstract

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.

2020-02-20
Language英语
DOI10.1155/2020/6734048
Source PublicationBIOMED RESEARCH INTERNATIONAL
ISSN2314-6133
Volume2020Pages:19
Subtypearticle
Indexed BySCI
Funding ProjectNational 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]
PublisherHINDAWI LTD
WOS KeywordGENOME-WIDE ANNOTATIONS ; RETINOIC ACID ; PARKINSONS-DISEASE ; NEUROTROPHIC FACTOR ; NEURONAL DIFFERENTIATION ; SYNAPTIC PLASTICITY ; SIGNALING PATHWAY ; CHRONIC STRESS ; SH-SY5Y CELLS ; EXPRESSION
WOS Research AreaBiotechnology & Applied Microbiology ; Research & Experimental Medicine
WOS SubjectBiotechnology & Applied Microbiology ; Medicine, Research & Experimental
WOS IDWOS:000518931800004
QuartileQ3
Citation statistics
Document Type期刊论文
Identifierhttp://ir.psych.ac.cn/handle/311026/31392
Collection中国科学院心理健康重点实验室
Corresponding AuthorWang, Jing
Affiliation1.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
First Author AffilicationKey Laboratory of Mental Health, CAS
Corresponding Author AffilicationKey Laboratory of Mental Health, CAS
Recommended Citation
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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