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Identification of RNA-Binding Proteins as Targetable Putative Oncogenes in Neuroblastoma
Neuroblastoma is a common childhood cancer with almost a third of those affected still dying, thus new therapeutic strategies need to be explored. Current experimental therapies focus mostly on inhibiting oncogenic transcription factor signalling. Although LIN28B, DICER and other RNA-binding protein...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403987/ https://www.ncbi.nlm.nih.gov/pubmed/32707690 http://dx.doi.org/10.3390/ijms21145098 |
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author | Bell, Jessica L. Hagemann, Sven Holien, Jessica K. Liu, Tao Nagy, Zsuzsanna Schulte, Johannes H. Misiak, Danny Hüttelmaier, Stefan |
author_facet | Bell, Jessica L. Hagemann, Sven Holien, Jessica K. Liu, Tao Nagy, Zsuzsanna Schulte, Johannes H. Misiak, Danny Hüttelmaier, Stefan |
author_sort | Bell, Jessica L. |
collection | PubMed |
description | Neuroblastoma is a common childhood cancer with almost a third of those affected still dying, thus new therapeutic strategies need to be explored. Current experimental therapies focus mostly on inhibiting oncogenic transcription factor signalling. Although LIN28B, DICER and other RNA-binding proteins (RBPs) have reported roles in neuroblastoma development and patient outcome, the role of RBPs in neuroblastoma is relatively unstudied. In order to elucidate novel RBPs involved in MYCN-amplified and other high-risk neuroblastoma subtypes, we performed differential mRNA expression analysis of RBPs in a large primary tumour cohort (n = 498). Additionally, we found via Kaplan–Meier scanning analysis that 685 of the 1483 tested RBPs have prognostic value in neuroblastoma. For the top putative oncogenic candidates, we analysed their expression in neuroblastoma cell lines, as well as summarised their characteristics and existence of chemical inhibitors. Moreover, to help explain their association with neuroblastoma subtypes, we reviewed candidate RBPs’ potential as biomarkers, and their mechanistic roles in neuronal and cancer contexts. We found several highly significant RBPs including RPL22L1, RNASEH2A, PTRH2, MRPL11 and AFF2, which remain uncharacterised in neuroblastoma. Although not all RBPs appear suitable for drug design, or carry prognostic significance, we show that several RBPs have strong rationale for inhibition and mechanistic studies, representing an alternative, but nonetheless promising therapeutic strategy in neuroblastoma treatment. |
format | Online Article Text |
id | pubmed-7403987 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-74039872020-08-11 Identification of RNA-Binding Proteins as Targetable Putative Oncogenes in Neuroblastoma Bell, Jessica L. Hagemann, Sven Holien, Jessica K. Liu, Tao Nagy, Zsuzsanna Schulte, Johannes H. Misiak, Danny Hüttelmaier, Stefan Int J Mol Sci Article Neuroblastoma is a common childhood cancer with almost a third of those affected still dying, thus new therapeutic strategies need to be explored. Current experimental therapies focus mostly on inhibiting oncogenic transcription factor signalling. Although LIN28B, DICER and other RNA-binding proteins (RBPs) have reported roles in neuroblastoma development and patient outcome, the role of RBPs in neuroblastoma is relatively unstudied. In order to elucidate novel RBPs involved in MYCN-amplified and other high-risk neuroblastoma subtypes, we performed differential mRNA expression analysis of RBPs in a large primary tumour cohort (n = 498). Additionally, we found via Kaplan–Meier scanning analysis that 685 of the 1483 tested RBPs have prognostic value in neuroblastoma. For the top putative oncogenic candidates, we analysed their expression in neuroblastoma cell lines, as well as summarised their characteristics and existence of chemical inhibitors. Moreover, to help explain their association with neuroblastoma subtypes, we reviewed candidate RBPs’ potential as biomarkers, and their mechanistic roles in neuronal and cancer contexts. We found several highly significant RBPs including RPL22L1, RNASEH2A, PTRH2, MRPL11 and AFF2, which remain uncharacterised in neuroblastoma. Although not all RBPs appear suitable for drug design, or carry prognostic significance, we show that several RBPs have strong rationale for inhibition and mechanistic studies, representing an alternative, but nonetheless promising therapeutic strategy in neuroblastoma treatment. MDPI 2020-07-19 /pmc/articles/PMC7403987/ /pubmed/32707690 http://dx.doi.org/10.3390/ijms21145098 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Bell, Jessica L. Hagemann, Sven Holien, Jessica K. Liu, Tao Nagy, Zsuzsanna Schulte, Johannes H. Misiak, Danny Hüttelmaier, Stefan Identification of RNA-Binding Proteins as Targetable Putative Oncogenes in Neuroblastoma |
title | Identification of RNA-Binding Proteins as Targetable Putative Oncogenes in Neuroblastoma |
title_full | Identification of RNA-Binding Proteins as Targetable Putative Oncogenes in Neuroblastoma |
title_fullStr | Identification of RNA-Binding Proteins as Targetable Putative Oncogenes in Neuroblastoma |
title_full_unstemmed | Identification of RNA-Binding Proteins as Targetable Putative Oncogenes in Neuroblastoma |
title_short | Identification of RNA-Binding Proteins as Targetable Putative Oncogenes in Neuroblastoma |
title_sort | identification of rna-binding proteins as targetable putative oncogenes in neuroblastoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403987/ https://www.ncbi.nlm.nih.gov/pubmed/32707690 http://dx.doi.org/10.3390/ijms21145098 |
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