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Series GSE81497 Query DataSets for GSE81497
Status Public on Jul 06, 2016
Title Multiple mechanisms disrupt let-7 miRNA biogenesis and function in neuroblastoma [Let7Targets]
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary The let-7 microRNA families are tumor suppressors often deregulated in cancer, yet the underlying mechanisms of let-7 disruption remain poorly understood. Neuroblastoma is defined in part by poor prognosis associated with genetic amplification of MYCN, itself a let-7 target. The let-7 biogenesis inhibitor LIN28B has been implicated as a critical regulator of MYCN ; however, here we show that LIN28B is dispensable for both MYCN protein expression and growth of MYCN amplified neuroblastoma cell lines despite robust de-repression of let-7 . We further report that amplified MYCN mRNA is a potent let-7 sponge that through exceptionally high expression defines a sub-set of self-sponging amplified competing endogenous RNA (aceRNA) and reconciles the dispensability of LIN28B . In addition, we observe frequent genomic loss of let-7 that inversely associates with MYCN- amplification, providing an explanation for common, yet unresolved amplification-independent patterns of chromosome loss. We thus propose a model whereby let-7 disruption by genetic loss, LIN28B expression, or aceRNA sponging is a unifying mechanism of neuroblastoma pathogenesis. Indeed, our data show that the majority of neuroblastomas have at least one let-7 disruption event and that genetic loss in non-MYCN amplified tumors marks decreased survival, further underscoring its importance. The inverse relationship between allelic loss and sponging of let-7 from highly expressed or amplified oncogenes may have broad implications for oncogenesis.
Overall design BE(2)C:MYCN-ORF cells transfected with siRNA and miRNA mimics
Contributor(s) Powers JT, Cahan P, Daley GQ
Citation(s) 27383785
Submission date May 17, 2016
Last update date May 15, 2019
Contact name Patrick Cahan
Organization name Johns Hopkins University School of Medicine
Department ICE and Biomedical Engineering
Lab Cahan Lab
Street address 733 North Broadway, MRB 653
City Baltimore
State/province MD
ZIP/Postal code 21205
Country USA
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (4)
GSM2154858 BE2C:MYCN siCon/miRCon
GSM2154859 BE2C:MYCN siCon/let-7a
GSM2154860 BE2C:MYCN siMYCN/miRCon
This SubSeries is part of SuperSeries:
GSE81500 Multiple mechanisms disrupt let-7 miRNA biogenesis and function in neuroblastoma
BioProject PRJNA321947
SRA SRP075356

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Supplementary file Size Download File type/resource
GSE81497_expJTP_let7Targets.csv.gz 431.0 Kb (ftp)(http) CSV
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