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
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Journal ArticleDOI
MYCN in Neuroblastoma: "Old Wine into New Wineskins".
TL;DR: In this article, the role of BHLH Transcription factor (myCN) in neuroblastoma has been investigated from all possible mechanistic sites, including the references of myCN in the literature, the gene's anatomy along with its transcripts, the protein's anatomy, the epigenetic mechanisms regulating MYCN expression and function, as well as MYCN amplification.
Journal ArticleDOI
miR-15a and miR-15b modulate natural killer and CD8+T-cell activation and anti-tumor immune response by targeting PD-L1 in neuroblastoma
Anup Singh Pathania,Philip Prathipati,Omalla A. Olwenyi,Srinivas Chava,OgheneTejiri V. Smith,Subash C. Gupta,Nagendra K. Chaturvedi,Siddappa N. Byrareddy,Don W. Coulter,Kishore B. Challagundla +9 more
TL;DR: In this paper , the role of micro RNAs in anti-tumor immune response via a range of data-driven workflows and in vitro & in vivo experiments was explored.
Journal ArticleDOI
A New Player in Neuroblastoma: YAP and Its Role in the Neuroblastoma Microenvironment.
Jenny Shim,Kelly C. Goldsmith +1 more
TL;DR: In this article, the authors focus on the role of YAP in neuroblastoma and further describe its demonstrated and potential effects on the solid tumor microenvironment (TME) and discuss the therapeutic strategies for inhibiting YAP.
Journal ArticleDOI
MYCN Impact on High-Risk Neuroblastoma: From Diagnosis and Prognosis to Targeted Treatment
Damiano Bartolucci,Luca Montemurro,Salvatore Raieli,Silvia Lampis,Andrea Pession,Patrizia Hrelia,Roberto Tonelli +6 more
TL;DR: The aim of this review is to describe the current knowledge in the diagnosis, prognosis and therapeutic approaches of HR-NB, particularly in relation to MYCN, to highlight how MYCN influences the HR- NB scenario and the new therapeutic approaches that are currently proposed to target it.
Journal ArticleDOI
IGF2BP1 induces neuroblastoma via a druggable feedforward loop with MYCN promoting 17q oncogene expression
Sven Hagemann,Danny Misiak,Jessica L. Bell,Tommy Fuchs,Marcell Lederer,Nadine Bley,Monika Hämmerle,Ehab Ghazy,Wolfgang Sippl,Johannes Schulz,Stefan Hüttelmaier +10 more
TL;DR: In this article , a druggable neuroblastoma oncogene circuit settling on strong, transcriptional/post-transcriptional synergy of MYCN and IGF2BP1 was investigated.
References
More filters
Journal ArticleDOI
Rapid identification of regulatory microRNAs by miTRAP (miRNA trapping by RNA in vitro affinity purification)
TL;DR: In this paper, the authors describe miTRAP (miRNA trapping by RNA in vitro affinity purification), an advanced protocol of previously reported MS2-tethering approaches that allows the rapid identification of miRNAs targeting an in vitro transcribed RNA in cell lysates.
Journal ArticleDOI
HuD Is a Neural Translation Enhancer Acting on mTORC1-Responsive Genes and Counteracted by the Y3 Small Non-coding RNA
Toma Tebaldi,Paola Zuccotti,Daniele Peroni,Marcel Köhn,Lisa Gasperini,Valentina Potrich,Veronica Bonazza,Tatiana Dudnakova,Annalisa Rossi,Guido Sanguinetti,Luciano Conti,Paolo Macchi,Vito Giuseppe D'Agostino,Gabriella Viero,David Tollervey,Stefan Hüttelmaier,Alessandro Quattrone +16 more
TL;DR: These findings uncover an alternative route to the mTORC1 pathway for translational control in motor neurons that is tunable by a small non-coding RNA.
Journal ArticleDOI
IGF2BP1 Harbors Prognostic Significance by Gene Gain and Diverse Expression in Neuroblastoma
TL;DR: It is demonstrated that IGF2BP1 is a potential oncogene and an independent negative prognostic factor in neuroblastoma and was associated with lower overall patient survival and MYCN abundance.
Journal ArticleDOI
Ribosomal RNA 2'O-methylation as a novel layer of inter-tumour heterogeneity in breast cancer.
Virginie Marcel,Janice Kielbassa,Virginie Marchand,Kundhavai S. Natchiar,Hermes Paraqindes,Flora Nguyen Van Long,Lilia Ayadi,Valérie Bourguignon-Igel,Piero Lo Monaco,Déborah Monchiet,Véronique Scott,Laurie Tonon,Susan E. Bray,Alexandra Diot,Lee B. Jordan,Alastair M. Thompson,Alastair M. Thompson,Jean-Christophe Bourdon,Thierry Dubois,Fabrice Andre,Frédéric Catez,Alain Puisieux,Yuri Motorin,Bruno P. Klaholz,Alain Viari,Jean-Jacques Diaz +25 more
TL;DR: In this paper, the authors established the first rRNA 2′O-methylation landscape in 195 primary human breast tumours and uncovered the existence of compulsory/stable sites, which show limited inter-patient variability in their 2'O'-methylation level, which are surrounded by variable sites found from the second nucleotide layers.
Journal ArticleDOI
Transcriptional Regulation of CRD-BP by c-myc: Implications for c-myc Functions.
TL;DR: It is shown that c- myc binds to CRD-BP promoter and induces its transcription, which contributes to the role of c-myc in the regulation of translation, increase in cell size, and acceleration of cell cycle progression via a mechanism involving upregulation of β-TrCP1 levels and activities and accelerated degradation of PDCD4.