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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 | |
第一作者 | Guo, Liyuan |
通讯作者邮箱 | wangjing@psych.ac.cn |
心理所单位排序 | 1 |
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. |
2020-02-20 | |
语种 | 英语 |
DOI | 10.1155/2020/6734048 |
发表期刊 | BIOMED RESEARCH INTERNATIONAL |
ISSN | 2314-6133 |
卷号 | 2020页码:19 |
期刊论文类型 | article |
收录类别 | SCI |
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] |
出版者 | HINDAWI LTD |
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 |
WOS研究方向 | Biotechnology & Applied Microbiology ; Research & Experimental Medicine |
WOS类目 | Biotechnology & Applied Microbiology ; Medicine, Research & Experimental |
WOS记录号 | WOS:000518931800004 |
Q分类 | Q3 |
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 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://ir.psych.ac.cn/handle/311026/31392 |
专题 | 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 |
第一作者单位 | 中国科学院心理健康重点实验室 |
通讯作者单位 | 中国科学院心理健康重点实验室 |
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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