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Updated: May 30, 2026

Development of Compendium for Esophageal Squamous Cell Carcinoma
Published on: April 12, 2024
Downregulation of RBMS3 is associated with poor prognosis in esophageal squamous cell carcinoma
Yan Li1, Leilei Chen, Chang-jun Nie
1State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-sen University, Guangzhou, China.
Abstract:
Deletions on chromosome 3p occur often in many solid tumors, including esophageal squamous cell carcinoma (ESCC), suggesting the existence at this location of one or more tumor suppressor genes (TSG). In this study, we characterized RBMS3 gene encoding an RNA-binding protein as a candidate TSG located at 3p24. Downregulation of RBMS3 mRNA and protein levels was documented in approximately 50% of the primary ESCCs examined. Clinical association studies determined that RBMS3 downregulation was associated with poor clinical outcomes. RBMS3 expression effectively suppressed the tumorigenicity of ESCC cells in vitro and in vivo, including by inhibition of cell growth rate, foci formation, soft agar colony formation, and tumor formation in nude mice. Molecular analyses revealed that RBMS3 downregulated c-Myc and CDK4, leading to subsequent inhibition of Rb phosphorylation. Together, our findings suggest a tumor suppression function for the human RBMS3 gene in ESCC, acting through c-Myc downregulation, with genetic loss of this gene in ESCC contributing to poor outcomes in this deadly disease.
Insights
RBMS3 acts as a tumor suppressor gene in esophageal squamous cell carcinoma (ESCC). Its downregulation is linked to poor outcomes, and restoring RBMS3 inhibits ESCC tumor growth.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Chromosome 3p deletions are common in solid tumors like esophageal squamous cell carcinoma (ESCC).
- This suggests the presence of tumor suppressor genes (TSGs) on chromosome 3p.
- RBMS3, an RNA-binding protein gene at 3p24, is investigated as a potential TSG.
Purpose of the Study:
- To characterize the RBMS3 gene as a candidate tumor suppressor gene in ESCC.
- To investigate the role of RBMS3 in ESCC tumorigenesis and its association with clinical outcomes.
Main Methods:
- RBMS3 mRNA and protein levels were analyzed in primary ESCC samples.
- Clinical association studies were performed to correlate RBMS3 expression with patient outcomes.
- In vitro and in vivo assays were used to assess the effect of RBMS3 on ESCC cell tumorigenicity.
- Molecular analyses were conducted to identify downstream targets of RBMS3.
Main Results:
- RBMS3 mRNA and protein were downregulated in approximately 50% of ESCCs.
- RBMS3 downregulation correlated with poor clinical outcomes in ESCC patients.
- Restoration of RBMS3 suppressed ESCC cell growth, colony formation, and tumor development in vivo.
- RBMS3 was found to downregulate c-Myc and CDK4, inhibiting Rb phosphorylation.
Conclusions:
- RBMS3 functions as a tumor suppressor gene in ESCC.
- RBMS3 exerts its tumor suppressive effects partly through c-Myc downregulation.
- Loss of RBMS3 contributes to poor prognosis in ESCC, highlighting its clinical significance.
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