Related Experiment Video
Updated: Apr 7, 2026
Characterization of Functionally Associated miRNAs in Glioblastoma and their Engineering into Artificial Clusters for Gene Therapy
Published on: October 4, 2019
RUVBL1 and RUVBL2 are druggable MYC effector regulators in neuroblastoma cells
Joachim Tetteh Siaw1,2,3, Arne Claeys1,2,3, Wei-Yun Lai3
1Department of Human Structure and Repair, Anatomy and Embryology Unit, Ghent University, Ghent, Belgium.
Abstract:
High-risk neuroblastoma is characterized by MYCN amplification and high MYCN or MYC gene expression. These patients have a poor prognosis and there is an urgent need for more effective drugs. While strategies to develop inhibitors that directly target the MYC proteins have remained largely unsuccessful, recent preclinical studies have identified ATR, a key protein of the DNA damage response, as a promising alternative therapeutic target. Here, we identified a strong RUVBL1 and RUVBL2 signature in transcriptomics data derived from different MYCN-driven mice tumors treated with ATR inhibitors. The RUVBL proteins form a complex with ATPase activity that has broad cellular functions and we demonstrate that pharmacological inhibition of this protein complex results in a strong reduction of MYC(N) signaling, cell-cycle arrest, DNA damage, and apoptosis. We confirmed the association with MYCN and identified the RUVBL genes as independent prognostic biomarkers in human primary neuroblastoma data.
Insights
Targeting RUVBL1 and RUVBL2 proteins shows promise for treating high-risk neuroblastoma by reducing MYC(N) signaling and inducing cell death. These RUVBL genes are also identified as potential biomarkers for patient prognosis.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- High-risk neuroblastoma features MYCN amplification and poor prognosis, necessitating novel therapeutic strategies.
- Directly targeting MYC proteins has proven challenging, shifting focus to alternative targets like ATR in DNA damage response.
- ATR inhibitors are being explored for neuroblastoma, with potential off-target effects or associated pathways needing investigation.
Purpose of the Study:
- To investigate the role of RUVBL1 and RUVBL2 in MYCN-driven neuroblastoma.
- To evaluate the therapeutic potential of inhibiting the RUVBL complex in neuroblastoma.
- To identify RUVBL genes as prognostic biomarkers in human neuroblastoma.
Main Methods:
- Transcriptomic analysis of MYCN-driven mouse tumors treated with ATR inhibitors.
- Pharmacological inhibition of the RUVBL1/RUVBL2 complex using small molecules.
- Assessment of MYC(N) signaling, cell-cycle progression, DNA damage, and apoptosis.
- Validation of RUVBL gene association with MYCN and prognostic significance in human neuroblastoma datasets.
Main Results:
- A significant RUVBL1 and RUVBL2 gene expression signature was identified in MYCN-driven tumors treated with ATR inhibitors.
- Pharmacological inhibition of the RUVBL complex effectively reduced MYC(N) signaling, induced cell-cycle arrest, DNA damage, and apoptosis.
- The RUVBL proteins were confirmed to associate with MYCN.
- RUVBL1 and RUVBL2 were identified as independent prognostic biomarkers in human primary neuroblastoma.
Conclusions:
- The RUVBL1/RUVBL2 complex is a critical mediator in MYCN-driven neuroblastoma and a viable therapeutic target.
- Inhibiting the RUVBL complex offers a promising strategy for treating high-risk neuroblastoma.
- RUVBL genes serve as valuable prognostic biomarkers for neuroblastoma patients.
Related Concept Videos
01:23Negative Regulator Molecules
01:03Rous Sarcoma Virus (RSV) and Cancer
01:03Rous Sarcoma Virus (RSV) and Cancer
RSV is a retrovirus that contains two copies of a plus-strand RNA genome. Its genome consists of four main open...
02:23Abnormal Proliferation