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Updated: Oct 18, 2025

Monitoring Protein-RNA Interaction Dynamics In Vivo at High Temporal Resolution Using χCRAC
Published on: May 9, 2020
RNA binding protein RBMS3 is a common EMT effector that modulates triple-negative breast cancer progression via
C James Block1, Allison V Mitchell1, Ling Wu1,2
1Barbara Ann Karmanos Cancer Institute, Department of Oncology, Wayne State University School of Medicine, 4100 John R, Detroit, MI, 48201, USA.
Abstract:
The epithelial-to-mesenchymal transition (EMT) has been recognized as a driving force for tumor progression in breast cancer. Recently, our group identified the RNA Binding Motif Single Stranded Interacting Protein 3 (RBMS3) to be significantly associated with an EMT transcriptional program in breast cancer. Additional expression profiling demonstrated that RBMS3 was consistently upregulated by multiple EMT transcription factors and correlated with mesenchymal gene expression in breast cancer cell lines. Functionally, RBMS3 was sufficient to induce EMT in two immortalized mammary epithelial cell lines. In triple-negative breast cancer (TNBC) models, RBMS3 was necessary for maintaining the mesenchymal phenotype and invasion and migration in vitro. Loss of RBMS3 significantly impaired both tumor progression and spontaneous metastasis in vivo. Using a genome-wide approach to interrogate mRNA stability, we found that ectopic expression of RBMS3 upregulates many genes that are resistant to degradation following transcriptional blockade by actinomycin D (ACTD). Specifically, RBMS3 was shown to interact with the mRNA of EMT transcription factor PRRX1 and promote PRRX1 mRNA stability. PRRX1 is required for RBMS3-mediated EMT and is partially sufficient to rescue the effect of RBMS3 knockdown in TNBC cell lines. Together, this study identifies RBMS3 as a novel and common effector of EMT, which could be a promising therapeutic target for TNBC treatment.
Insights
RNA Binding Motif Single Stranded Interacting Protein 3 (RBMS3) drives breast cancer progression and metastasis by promoting the epithelial-to-mesenchymal transition (EMT). Targeting RBMS3 may offer a new therapeutic strategy for triple-negative breast cancer (TNBC).
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Epithelial-to-mesenchymal transition (EMT) is a key driver of tumor progression in breast cancer.
- The role of RNA Binding Motif Single Stranded Interacting Protein 3 (RBMS3) in EMT and breast cancer has not been fully elucidated.
Purpose of the Study:
- To investigate the function of RBMS3 in breast cancer, particularly in triple-negative breast cancer (TNBC).
- To determine if RBMS3 is a potential therapeutic target for TNBC.
Main Methods:
- Expression profiling in breast cancer cell lines.
- Functional assays in immortalized mammary epithelial cell lines and TNBC models.
- Genome-wide mRNA stability analysis.
- Interaction studies between RBMS3 and PRRX1 mRNA.
Main Results:
- RBMS3 is upregulated by EMT transcription factors and correlates with mesenchymal gene expression.
- RBMS3 induces EMT and maintains the mesenchymal phenotype, invasion, and migration in TNBC models.
- Loss of RBMS3 impairs tumor progression and metastasis in vivo.
- RBMS3 enhances the stability of target mRNAs, including PRRX1, a key EMT transcription factor.
Conclusions:
- RBMS3 is a novel and common effector of EMT in breast cancer.
- RBMS3 plays a critical role in maintaining the mesenchymal phenotype and promoting metastasis in TNBC.
- RBMS3 represents a promising therapeutic target for TNBC treatment.
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