Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Identifying master regulators that drive pathologic gene expression is a key challenge in precision oncology. Here, we have developed an analytic framework, named PRADA, that identifies oncogenic RNA-binding proteins through the systematic detection of coordinated changes in their target regulons. Application of this approach to data collected from clinical samples, patient-derived xenografts, and cell line models of colon cancer metastasis revealed the RNA-binding protein RBMS1 as a suppressor of colon cancer progression. We observed that silencing RBMS1 results in increased metastatic capacity in xenograft mouse models, and that restoring its expression blunts metastatic liver colonization. We have found that RBMS1 functions as a posttranscriptional regulator of RNA stability by directly binding its target mRNAs. Together, our findings establish a role for RBMS1 as a previously unknown regulator of RNA stability and as a suppressor of colon cancer metastasis with clinical utility for risk stratification of patients. SIGNIFICANCE: By applying a new analytic approach to transcriptomic data from clinical samples and models of colon cancer progression, we have identified RBMS1 as a suppressor of metastasis and as a post-transcriptional regulator of RNA stability. Notably, RBMS1 silencing and downregulation of its targets are negatively associated with patient survival.See related commentary by Carter, p. 1261.This article is highlighted in the In This Issue feature, p. 1241.
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PMID:RBMS1 Suppresses Colon Cancer Metastasis through Targeted Stabilization of Its mRNA Regulon. 3287 19

Yu and colleagues combined computational and experimental techniques to identify a new post-transcriptional regulator of metastatic potential in colon cancer. This study reveals that the RNA-binding protein RBMS1 is a positive regulator of mRNA stability for multiple genes, including the tumor suppressor AKAP12 and a WNT pathway interacting protein, SDCBP, and its loss is a common event associated with poor prognosis.See related article by Yu et al., p. 1410.
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PMID:Loss of RNA-Binding Protein RBMS1 Promotes a Metastatic Transcriptional Program in Colorectal Cancer. 3251 75