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RBMS1 Suppresses Colon Cancer Metastasis through Targeted Stabilization of Its mRNA Regulon
Johnny Yu1,2,3, Albertas Navickas1,2,3, Hosseinali Asgharian1,2,3
1Department of Biochemistry & Biophysics, University of California, San Francisco, San Francisco, California.
Cancer Discovery
|June 10, 2020
Summary
We identified RBMS1 as a suppressor of colon cancer metastasis using a new analytic framework. Silencing RBMS1 increased metastasis, while restoring its expression reduced it, highlighting its role in RNA stability.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Identifying master regulators of pathologic gene expression is crucial for precision oncology.
- RNA-binding proteins play significant roles in regulating gene expression.
Purpose of the Study:
- To develop an analytic framework (PRADA) for identifying oncogenic RNA-binding proteins.
- To investigate the role of RBMS1 in colon cancer metastasis.
Main Methods:
- Developed the PRADA analytic framework to detect coordinated changes in RNA-binding protein target regulons.
- Applied PRADA to transcriptomic data from colon cancer clinical samples, xenografts, and cell lines.
- Investigated the functional role of RBMS1 in metastasis using xenograft mouse models.
Main Results:
- Identified RBMS1 as a suppressor of colon cancer progression.
- RBMS1 silencing increased metastatic capacity in mouse models.
- RBMS1 directly binds target mRNAs, regulating RNA stability and suppressing metastasis.
- RBMS1 downregulation is associated with reduced patient survival.
Conclusions:
- RBMS1 is a novel suppressor of colon cancer metastasis and a post-transcriptional regulator of RNA stability.
- RBMS1 has potential clinical utility for stratifying patient risk in colon cancer.
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