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Status |
Public on Jul 22, 2020 |
Title |
LIN28B Regulates Transcription and Potentiates MYCN-induced Neuroblastoma in a let-7-independent Manner [RNA-seq] |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
LIN28B is highly expressed in neuroblastoma and promotes tumorigenesis at least in part through inhibition of let-7 microRNA biogenesis. Here, we report that overexpression of either wild-type LIN28B, or a LIN28B mutant that is unable to bind and inhibit let-7, accelerates the onset and increases the penetrance of MYCN-induced neuroblastoma, potentiates the invasion and migration of transformed sympathetic neuroblasts and drives the distant metastases in vivo. Genome-wide ChIP-seq analysis and co-immunoprecipitation experiments show that LIN28B indirectly binds active gene promoters in neuroblastoma cells through an interaction with ZNF143 and activates the expression of downstream targets, including GSK3B and L1CAM, which are involved in neuronal cell adhesion and migration. These findings reveal an unexpected, let-7-independent function for LIN28B in transcriptional regulation during neuroblastoma pathogenesis.
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Overall design |
RNA-Seq for BE2C cells engineered with a doxycycline-inducible overexpression of wild-type or mutant LIN28B, untreated (nDox) or treated (yDox) with doxycycline
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Contributor(s) |
Tao T, Shi H, Mariani L, Abraham BJ, Durbin AD, Zimmerman MW, Powers JT, Missios P, Ross KN, Perez-Atayde AR, Bulyk ML, Young RA, Daley GQ, Look AT |
Citation(s) |
32601179 |
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Submission date |
Oct 10, 2019 |
Last update date |
Jul 22, 2020 |
Contact name |
Ting Tao |
E-mail(s) |
taot@zju.edu.cn
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Organization name |
Children's Hospital, Zhejiang University School of Medicine
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Lab |
Ting Tao
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Street address |
3333 Binsheng Road
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City |
Hangzhou |
State/province |
Zhejiang |
ZIP/Postal code |
310052 |
Country |
China |
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Platforms (1) |
GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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Samples (11)
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This SubSeries is part of SuperSeries: |
GSE138743 |
LIN28B Regulates Transcription and Potentiates MYCN-induced Neuroblastoma in a let-7-independent Manner |
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Relations |
BioProject |
PRJNA576945 |
SRA |
SRP225128 |