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Updated: Sep 14, 2025
In vivo Interrogation of Central Nervous System Translatome by Polyribosome Fractionation
Published on: April 30, 2014
Ribosome biogenesis is a therapeutic vulnerability in pediatric neuroblastoma
Camille Jouines1, Piero Lo Monaco1, Angéline Gaucherot1
1Ribosome, Traduction and Cancer team, LabEx DEVweCAN, Institut Convergence Plascan, LyriCAN+, INCa PediacriEx SouthROCK, Centre de Recherche en Cancérologie de Lyon (CRCL), INSERM U1052, CNRS UMR 5286, Centre Léon Bérard, Université de Lyon, Université Claude Bernard Lyon 1, 69008, Lyon, France.
Abstract:
Neuroblastoma is a heterogeneous malignant pediatric tumor, the prognosis of which depends on patient age and disease stage. Current treatment strategies rely on four key diagnostic criteria: age, histological stage, genomic profile, and MYCN gene status. The oncogenic activity of MYC depends on ribosome biogenesis, which is hyperactivated in cancer cells to support their high proliferative capacity, and which may thus represent a vulnerability in neuroblastoma and constitute a therapeutic target. Here, using the well-established IMR-32 cell line along with a previously established panel of patient-derived neuroblastoma cell lines with varying MYCN status, we show that RNA polymerase I inhibition following exposure to CX-5461 and BMH-21 suppressed cell proliferation at nanomolar concentrations and induced ribosomal stress, leading to the activation of apoptosis and the p21 pathway. Furthermore, analysis of expression of ribosome biogenesis factors using publicly available datasets and RT-qPCR data from an in-house neuroblastoma cohort, we identified FBL as a marker of poor prognosis in neuroblastoma. Consistently, FBL knockdown reduced neuroblastoma cell proliferation, supporting its relevance as a therapeutic target. In conclusion, our study reinforces the therapeutic potential of ribosome biogenesis inhibition in neuroblastoma and expands the list of potential targets to include rRNA maturation factors. These findings highlight the relevance of targeting ribosome biogenesis as a novel approach for neuroblastoma treatment.
Insights
Targeting ribosome biogenesis, crucial for cancer cell proliferation, offers a new therapeutic strategy for neuroblastoma. Inhibiting RNA polymerase I and targeting FBL shows promise in suppressing tumor growth and activating apoptosis.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genetics
Background:
- Neuroblastoma is a complex pediatric cancer with prognosis dependent on age, stage, and genetic factors like MYCN.
- MYC oncogene activity relies on hyperactivated ribosome biogenesis, a potential vulnerability in cancer cells.
- Current treatments for neuroblastoma consider age, histology, genomic profile, and MYCN status.
Purpose of the Study:
- To investigate the therapeutic potential of inhibiting ribosome biogenesis in neuroblastoma.
- To identify novel therapeutic targets within the ribosome biogenesis pathway.
- To evaluate the role of Fibrillarin (FBL) as a prognostic marker and therapeutic target in neuroblastoma.
Main Methods:
- Utilized IMR-32 and patient-derived neuroblastoma cell lines with varying MYCN status.
- Administered RNA polymerase I inhibitors (CX-5461, BMH-21) to assess effects on cell proliferation and apoptosis.
- Analyzed ribosome biogenesis factor expression using public datasets and in-house cohort RT-qPCR data.
- Performed Fibrillarin (FBL) knockdown experiments to evaluate its impact on neuroblastoma cell proliferation.
Main Results:
- RNA polymerase I inhibition suppressed neuroblastoma cell proliferation at nanomolar concentrations, inducing ribosomal stress, apoptosis, and p21 pathway activation.
- Fibrillarin (FBL) was identified as a marker of poor prognosis in neuroblastoma.
- FBL knockdown significantly reduced neuroblastoma cell proliferation, confirming its relevance as a therapeutic target.
Conclusions:
- Ribosome biogenesis inhibition is a promising therapeutic strategy for neuroblastoma.
- Fibrillarin (FBL) represents a novel therapeutic target in neuroblastoma treatment.
- Targeting rRNA maturation factors offers expanded therapeutic avenues for neuroblastoma.
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