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Published on: March 5, 2013
Multi-omics profiling reveals dysregulated ribosome biogenesis and impaired cell proliferation following knockout of
Eirik Tveit Solheim1,2, Yola Gerking3,4, Torbjørn Kråkenes4,5
1Department of Clinical Medicine, University of Bergen, Bergen, Norway. eirik.t.solheim@uib.no.
Background:
Cerebellar degeneration-related (CDR) proteins are associated with paraneoplastic cerebellar degeneration (PCD) - a rare, neurodegenerative disease caused by tumour-induced autoimmunity against neural antigens resulting in degeneration of Purkinje neurons in the cerebellum. The pathogenesis of PCD is unknown, in large part due to our limited understanding of the functions of CDR proteins. To this end, we performed an extensive, multi-omics analysis of CDR-knockout cells focusing on the CDR2L protein, to gain a deeper understanding of the properties of the CDR proteins in ovarian cancer.
Methods:
Ovarian cancer cell lines lacking either CDR1, CDR2, or CDR2L were analysed using RNA sequencing and mass spectrometry-based proteomics to assess changes to the transcriptome, proteome and secretome in the absence of these proteins.
Results:
For each knockout cell line, we identified sets of differentially expressed genes and proteins. CDR2L-knockout cells displayed a distinct expression profile compared to CDR1- and CDR2-knockout cells. Knockout of CDR2L caused dysregulation of genes involved in ribosome biogenesis, protein translation, and cell cycle progression, ultimately causing impaired cell proliferation in vitro. Several of these genes showed a concurrent upregulation at the transcript level and downregulation at the protein level.
Conclusions:
Our study provides the first integrative multi-omics analysis of the impact of knockout of the CDR genes, providing both new insights into the biological properties of the CDR proteins in ovarian cancer, and a valuable resource for future investigations into the CDR proteins.
Insights
Investigating Cerebellar degeneration-related (CDR) proteins in ovarian cancer, this study found that CDR2L knockout impairs cell proliferation by disrupting ribosome biogenesis and protein translation. This research offers new insights into CDR protein functions.
Area of Science:
- Oncology
- Neuroimmunology
- Molecular Biology
Background:
- Cerebellar degeneration-related (CDR) proteins are linked to paraneoplastic cerebellar degeneration (PCD), a rare autoimmune disorder affecting Purkinje neurons.
- The exact functions of CDR proteins in PCD pathogenesis remain largely unknown.
- Ovarian cancer can trigger PCD through anti-neural autoimmunity.
Purpose of the Study:
- To elucidate the biological functions of CDR proteins in ovarian cancer.
- To investigate the impact of CDR gene knockout on cellular processes using multi-omics analysis.
- To specifically focus on the role of CDR2L in ovarian cancer cells.
Main Methods:
- Utilized RNA sequencing and mass spectrometry-based proteomics on ovarian cancer cell lines.
- Created cell lines lacking CDR1, CDR2, or CDR2L.
- Analyzed changes in the transcriptome, proteome, and secretome following gene knockout.
Main Results:
- Identified distinct gene and protein expression profiles for each CDR knockout cell line.
- CDR2L knockout led to dysregulation of ribosome biogenesis, protein translation, and cell cycle genes.
- CDR2L deficiency resulted in impaired in vitro cell proliferation, with some genes showing differential transcript and protein level changes.
Conclusions:
- This study presents the first integrated multi-omics analysis of CDR gene knockout effects in ovarian cancer.
- Provides novel insights into the biological roles of CDR proteins within the context of ovarian cancer.
- Establishes a foundational resource for future research on CDR proteins and their implications in disease.
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