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
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Journal ArticleDOI
Recent advances in neuroblastoma.
TL;DR: The author discusses recent advances in the understanding of neuroblastoma, an embryonal cancer of the autonomic nervous system, which has one of the highest rates of spontaneous and complete regression.
Journal ArticleDOI
miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis
Li Ma,Jennifer J. Young,Harsha K. Prabhala,Elizabeth Pan,Pieter Mestdagh,Daniel Muth,Julie Teruya-Feldstein,Ferenc Reinhardt,Tamer T. Onder,Scott Valastyan,Frank Westermann,Frank Speleman,Jo Vandesompele,Robert A. Weinberg +13 more
TL;DR: It is shown that miR-9, which is upregulated in breast cancer cells, directly targets CDH1, the E-cadherin-encoding messenger RNA, leading to increased cell motility and invasiveness, and a regulatory and signalling pathway involving a metastasis-promoting miRNA that is predicted to directly target expression of the key metastasis
Journal ArticleDOI
Neuroblastoma: Biology, Prognosis, and Treatment
TL;DR: This article summarizes the understanding of neuroblastoma biology and prognostic features and discusses their impact on current and proposed risk stratification schemas, risk-based therapeutic approaches, and the development of novel therapies for patients at high risk for failure.
Journal ArticleDOI
Insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs): post-transcriptional drivers of cancer progression?
Jessica L. Bell,Kristin Wächter,Britta Mühleck,Nikolaos Pazaitis,Marcel Köhn,Marcell Lederer,Stefan Hüttelmaier +6 more
TL;DR: The IGF2BP family’s role in cancer biology is discussed and how this correlates with their proposed functions during embryogenesis is discussed, which could provide valuable targets in cancer treatment with many of their in vivo roles to be fully elucidated.
Journal ArticleDOI
Neuroblastoma and MYCN
Miller Huang,William A. Weiss +1 more
TL;DR: Roles for MYCN in neuroblastoma are reviewed and recent identification of other driver mutations are highlighted, as well as strategies to target MYCN at the level of protein stability and transcription.