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- W3008123952 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." @default.
- W3008123952 created "2020-03-06" @default.
- W3008123952 creator A5024000389 @default.
- W3008123952 creator A5026192569 @default.
- W3008123952 creator A5037677450 @default.
- W3008123952 creator A5045411384 @default.
- W3008123952 date "2020-02-20" @default.
- W3008123952 modified "2023-10-16" @default.
- W3008123952 title "A Systematic Analysis Revealed the Potential Gene Regulatory Processes of ATRA-Triggered Neuroblastoma Differentiation and Identified a Novel RA Response Sequence in theNTRK2Gene" @default.
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- W3008123952 doi "https://doi.org/10.1155/2020/6734048" @default.
- W3008123952 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7053487" @default.
- W3008123952 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/32149119" @default.
- W3008123952 hasPublicationYear "2020" @default.
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