The MicroRNA Landscape of MYCN-Amplified Neuroblastoma.
Danny Misiak,Sven Hagemann,Jessica L. Bell,Bianca Busch,Marcell Lederer,Nadine Bley,Johannes H. Schulte,Stefan Hüttelmaier +7 more
TLDR
In this paper, the miRNome of 97 neuroblastoma-derived cells was analyzed using microRNA trapping by RNA affinity purification to reveal the MYCN-dependent miRNOME.Abstract:
MYCN gene amplification and upregulated expression are major hallmarks in the progression of high-risk neuroblastoma. MYCN expression and function in modulating gene synthesis in neuroblastoma is controlled at virtually every level, including poorly understood regulation at the post-transcriptional level. MYCN modulates the expression of various microRNAs including the miR-17-92 cluster. MYCN mRNA expression itself is subjected to the control by miRNAs, most prominently the miR-17-92 cluster that balances MYCN expression by feed-back regulation. This homeostasis seems disturbed in neuroblastoma where MYCN upregulation coincides with severely increased expression of the miR-17-92 cluster. In the presented study, we applied high-throughput next generation sequencing to unravel the miRNome in a cohort of 97 neuroblastomas, representing all clinical stages. Aiming to reveal the MYCN-dependent miRNome, we evaluate miRNA expression in MYCN-amplified as well as none amplified tumor samples. In correlation with survival data analysis of differentially expressed miRNAs, we present various putative oncogenic as well as tumor suppressive miRNAs in neuroblastoma. Using microRNA trapping by RNA affinity purification, we provide a comprehensive view of MYCN-regulatory miRNAs in neuroblastoma-derived cells, confirming a pivotal role of the miR-17-92 cluster and moderate association by the let-7 miRNA family. Attempting to decipher how MYCN expression escapes elevated expression of inhibitory miRNAs, we present evidence that RNA-binding proteins like the IGF2 mRNA binding protein 1 reduce miRNA-directed downregulation of MYCN in neuroblastoma. Our findings emphasize the potency of post-transcriptional regulation of MYCN in neuroblastoma and unravel new avenues to pursue inhibition of this potent oncogene.read more
Citations
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Bioinformatics analysis of miRNAs in the neuroblastoma 11q-deleted region reveals a role of miR-548l in both 11q-deleted and MYCN amplified tumour cells
TL;DR: In this paper , the miR-548l level was found to suppress cell viability and inhibited apoptosis in neuroblastoma cells and showed that miR−548l overexpression suppressed cell viability.
Posted ContentDOI
IGF2BP1 induces high-risk neuroblastoma and forms a druggable feedforward loop with MYCN promoting 17q oncogene expression
TL;DR: In this article , the authors reveal a druggable feed-forward loop of IGF2BP1 (17q) and MYCN (2p) in high-risk neuroblastoma.
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