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RNA Pull-down Procedure to Identify RNA Targets of a Long Non-coding RNA
Published on: April 10, 2018
Identification of RNA-Binding Proteins as Targetable Putative Oncogenes in Neuroblastoma
Jessica L Bell1,2, Sven Hagemann1, Jessica K Holien3,4
1Institute of Molecular Medicine, Sect. Molecular Cell Biology, Martin Luther University Halle-Wittenberg, Charles Tanford Protein Center, 06120 Halle Saale, Germany.
Abstract:
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.
Insights
This study identifies novel RNA-binding proteins (RBPs) as potential therapeutic targets for high-risk neuroblastoma. Several RBPs show prognostic value and warrant further investigation for drug development in this childhood cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Neuroblastoma is a prevalent childhood cancer with a high mortality rate, necessitating novel therapeutic approaches.
- Current treatments often target oncogenic transcription factors, but the role of RNA-binding proteins (RBPs) in neuroblastoma remains underexplored.
- Understanding RBPs is crucial for developing new strategies against high-risk neuroblastoma subtypes, such as those with MYCN amplification.
Purpose of the Study:
- To identify novel RNA-binding proteins (RBPs) implicated in the development of MYCN-amplified and other high-risk neuroblastoma.
- To assess the prognostic significance of RBPs in neuroblastoma patient outcomes.
- To explore the potential of identified RBPs as therapeutic targets and biomarkers for neuroblastoma.
Main Methods:
- Differential mRNA expression analysis was performed on a cohort of 498 primary neuroblastoma tumors.
- Kaplan-Meier scanning analysis was used to evaluate the prognostic value of 1483 tested RBPs.
- Expression analysis in neuroblastoma cell lines, literature review of candidate RBPs' characteristics, inhibitor availability, biomarker potential, and mechanistic roles were conducted.
Main Results:
- 685 out of 1483 tested RBPs demonstrated prognostic value in neuroblastoma.
- Several RBPs, including RPL22L1, RNASEH2A, PTRH2, MRPL11, and AFF2, were identified as highly significant but uncharacterized in neuroblastoma.
- The study identified specific RBPs with strong potential for targeted inhibition and mechanistic investigation.
Conclusions:
- RNA-binding proteins represent a promising, yet relatively unstudied, class of therapeutic targets for neuroblastoma.
- Specific RBPs show significant prognostic value and mechanistic rationale for further investigation in neuroblastoma treatment.
- Targeting RBPs offers an alternative therapeutic strategy for neuroblastoma, potentially improving outcomes for high-risk patients.
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