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RBM5 Acts as Tumor Suppressor in Medulloblastoma through Regulating Wnt/β-Catenin Signaling
Jianzhong Yu1, Guangchun Ji2, Wei Shi1
1Department of Neurosurgery, Children's Hospital of Fudan University, Shanghai, China.
Introduction:
RBM5 acts as a tumor suppressor gene in lung and breast cancers; however, its role in the pathogenesis of medulloblastoma (MB) remains unclear. We previously identified 4 RBM5 mutations in whole exome sequencing analysis of 40 MB patients. This study examined the role of RBM5 in MB progression.
Methods:
The expression patterns of RBM5 in tissues of 40 MB patients were analyzed using immunohistochemistry. Associations between RBM5 expression and overall survival (OS) were evaluated using Kaplan-Meier analysis. The RBM5 role in Daoy cells' proliferation, migration, and Wnt/β-catenin signaling was analyzed after RBM5 knockdown and overexpression.
Results:
The expression level of RBM5 mRNA and protein was significantly lower in MB than that in adjacent normal control tissues, and low RBM5 expression was significantly associated with reduced OS (p = 0.034). RBM5 knockdown induced Daoy and ONS-76 cells proliferation, while RBM5 overexpression repressed cell proliferation and migration in vitro (all p < 0.05). β-Catenin, LEF1, and cyclin D1 mRNA levels were upregulated, while DKK1 expression was downregulated in Daoy cells following RBM5 knockdown.
Conclusion:
RBM5 may function as a tumor suppressor in MB by regulating Wnt/β-catenin signaling, and its reduced expression is associated with lower OS.
Insights
RNA-binding protein 5 (RBM5) acts as a tumor suppressor in medulloblastoma (MB). Lower RBM5 expression correlates with reduced overall survival in MB patients, suggesting a role in disease progression.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The tumor suppressor role of RNA-binding protein 5 (RBM5) is established in lung and breast cancers.
- Its specific function in medulloblastoma (MB) pathogenesis is not well understood.
- Previous exome sequencing identified RBM5 mutations in 40 MB patients.
Purpose of the Study:
- To investigate the role of RBM5 in medulloblastoma (MB) progression.
- To analyze the association between RBM5 expression levels and patient survival.
- To determine the impact of RBM5 on MB cell behavior and signaling pathways.
Main Methods:
- Immunohistochemistry was used to analyze RBM5 expression in 40 MB patient tissues.
- Kaplan-Meier analysis assessed the correlation between RBM5 expression and overall survival (OS).
- RBM5 knockdown and overexpression experiments in Daoy and ONS-76 cells evaluated effects on proliferation, migration, and Wnt/β-catenin signaling.
Main Results:
- RBM5 mRNA and protein levels were significantly lower in MB tissues compared to normal controls.
- Low RBM5 expression was significantly associated with reduced OS (p = 0.034).
- RBM5 knockdown increased proliferation in MB cells, while RBM5 overexpression inhibited proliferation and migration in vitro. Wnt/β-catenin pathway components were altered upon RBM5 modulation.
Conclusions:
- RBM5 functions as a tumor suppressor in medulloblastoma (MB).
- Reduced RBM5 expression is linked to poorer overall survival in MB patients.
- RBM5 appears to regulate MB progression, potentially through the Wnt/β-catenin signaling pathway.
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