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Updated: Apr 30, 2026
Molecular Profiling of the Invasive Tumor Microenvironment in a 3-Dimensional Model of Colorectal Cancer Cells and Ex vivo Fibroblasts
Published on: April 29, 2014
An integrative analysis of colon cancer identifies an essential function for PRPF6 in tumor growth
Adam S Adler1, Mark L McCleland1, Sharon Yee2
1Department of Pathology.
Abstract:
The spliceosome machinery is composed of multimeric protein complexes that generate a diverse repertoire of mRNA through coordinated splicing of heteronuclear RNAs. While somatic mutations in spliceosome components have been discovered in several cancer types, the molecular bases and consequences of spliceosome aberrations in cancer are poorly understood. Here we report for the first time that PRPF6, a member of the tri-snRNP (small ribonucleoprotein) spliceosome complex, drives cancer proliferation by preferential splicing of genes associated with growth regulation. Inhibition of PRPF6 and other tri-snRNP complex proteins, but not other snRNP spliceosome complexes, selectively abrogated growth in cancer cells with high tri-snRNP levels. High-resolution transcriptome analyses revealed that reduced PRPF6 alters the constitutive and alternative splicing of a discrete number of genes, including an oncogenic isoform of the ZAK kinase. These findings implicate an essential role for PRPF6 in cancer via splicing of distinct growth-related gene products.
Insights
PRPF6, a spliceosome component, drives cancer growth by altering gene splicing. Inhibiting PRPF6 selectively stops cancer cell proliferation, highlighting its role in cancer via growth-related gene splicing.
Area of Science:
- Molecular Biology
- Cancer Research
- RNA Splicing
Background:
- The spliceosome machinery is crucial for mRNA diversity through RNA splicing.
- Somatic mutations in spliceosome components occur in cancer, but their roles are unclear.
Purpose of the Study:
- To investigate the role of PRPF6, a tri-snRNP spliceosome component, in cancer proliferation.
- To understand the molecular mechanisms by which PRPF6 influences cancer growth.
Main Methods:
- Analysis of PRPF6 function in cancer cell proliferation.
- High-resolution transcriptome analysis to identify PRPF6-regulated splicing events.
- Selective inhibition of spliceosome components in cancer cells.
Main Results:
- PRPF6 drives cancer proliferation through preferential splicing of growth-regulatory genes.
- Inhibition of PRPF6 and other tri-snRNP proteins selectively halts growth in cancer cells with high tri-snRNP levels.
- Reduced PRPF6 alters splicing of key genes, including an oncogenic ZAK kinase isoform.
Conclusions:
- PRPF6 plays an essential role in cancer by splicing specific growth-related gene products.
- Targeting PRPF6 and tri-snRNP proteins offers a potential therapeutic strategy for cancers with high tri-snRNP levels.
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