RNA-binding protein SORBS2 suppresses clear cell renal cell carcinoma metastasis by enhancing MTUS1 mRNA stability
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Updated: Nov 26, 2025

Desthiobiotin-Streptavidin-Affinity Mediated Purification of RNA-Interacting Proteins in Mesothelioma Cells
Published on: April 25, 2018
1Department of Medical Imaging, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China.
Abstract:
RNA-binding proteins (RBPs) predominantly contribute to abnormal posttranscriptional gene modulation and disease progression in cancer. Sorbin and SH3 domain-containing 2 (SORBS2), an RBP, has been reported to be a potent tumor suppressor in several cancer types. Through integrative analysis of clinical specimens, we disclosed that the expression level of SORBS2 was saliently decreased in metastatic tissues and positively correlated with overall survival. We observed that overexpression of SORBS2 brought about decreased metastatic capacity in ccRCC cell lines. Transcriptome-wide analysis revealed that SORBS2 notably increased microtubule-associated tumor-suppressor 1 gene (MTUS1) expression. In-depth mechanistic exploring discovered that the Cys2-His2 zinc finger (C2H2-ZnF) domain of SORBS2 directly bound to the 3' untranslated region (3'UTR) of MTUS1 mRNA, which increased MTUS1 mRNA stability. In addition, we identified that MTUS1 regulated microtubule dynamics via promoting KIF2CS192 phosphorylation by Aurora B. Together, our research identified SORBS2 as a suppressor of ccRCC metastasis by enhancing MTUS1 mRNA stability, providing a novel understanding of RBPs during ccRCC progression.
Insights
Sorbin and SH3 domain-containing 2 (SORBS2) suppresses kidney cancer metastasis by increasing microtubule-associated tumor-suppressor 1 (MTUS1) mRNA stability. This RNA-binding protein enhances MTUS1 expression, inhibiting cancer cell spread.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- RNA-binding proteins (RBPs) are crucial in posttranscriptional gene regulation and cancer progression.
- Sorbin and SH3 domain-containing 2 (SORBS2) functions as a tumor suppressor in various cancers.
- Decreased SORBS2 expression correlates with metastasis and poorer survival in kidney cancer.
Purpose of the Study:
- To investigate the role of SORBS2 in clear cell renal cell carcinoma (ccRCC) metastasis.
- To elucidate the molecular mechanisms by which SORBS2 affects ccRCC progression.
Main Methods:
- Integrative analysis of clinical specimens.
- Overexpression studies in ccRCC cell lines.
- Transcriptome-wide analysis to identify SORBS2 targets.
- RNA immunoprecipitation and mRNA stability assays.
- Western blotting and phosphorylation analysis.
Main Results:
- SORBS2 expression is significantly reduced in metastatic ccRCC tissues and linked to overall survival.
- Overexpressing SORBS2 reduces metastatic potential in ccRCC cells.
- SORBS2 directly binds to the 3' untranslated region of MTUS1 mRNA, enhancing its stability.
- MTUS1 promotes KIF2C phosphorylation, influencing microtubule dynamics.
Conclusions:
- SORBS2 acts as a suppressor of ccRCC metastasis by stabilizing MTUS1 mRNA.
- The SORBS2-MTUS1 axis offers a novel therapeutic target for ccRCC.
- Understanding RBP functions provides new insights into ccRCC progression.
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