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Updated: Jul 26, 2025

Genome-wide Protein-protein Interaction Screening by Protein-fragment Complementation Assay PCA in Living Cells
Published on: March 3, 2015
Multi-Omic Analysis of CIC's Functional Networks Reveals Novel Interaction Partners and a Potential Role in Mitotic
Yuka Takemon1,2, Véronique G LeBlanc2, Jungeun Song2
1Genome Science and Technology Graduate Program, University of British Columbia, Vancouver, BC V5Z 4S6, Canada.
Abstract:
CIC encodes a transcriptional repressor and MAPK signalling effector that is inactivated by loss-of-function mutations in several cancer types, consistent with a role as a tumour suppressor. Here, we used bioinformatic, genomic, and proteomic approaches to investigate CIC's interaction networks. We observed both previously identified and novel candidate interactions between CIC and SWI/SNF complex members, as well as novel interactions between CIC and cell cycle regulators and RNA processing factors. We found that CIC loss is associated with an increased frequency of mitotic defects in human cell lines and an in vivo mouse model and with dysregulated expression of mitotic regulators. We also observed aberrant splicing in CIC-deficient cell lines, predominantly at 3' and 5' untranslated regions of genes, including genes involved in MAPK signalling, DNA repair, and cell cycle regulation. Our study thus characterises the complexity of CIC's functional network and describes the effect of its loss on cell cycle regulation, mitotic integrity, and transcriptional splicing, thereby expanding our understanding of CIC's potential roles in cancer. In addition, our work exemplifies how multi-omic, network-based analyses can be used to uncover novel insights into the interconnected functions of pleiotropic genes/proteins across cellular contexts.
Insights
Loss of the CIC tumor suppressor disrupts cell division and RNA splicing. This study reveals CIC’s network interactions and its role in maintaining genomic stability, offering new cancer insights.
Area of Science:
- * Molecular Biology
- * Cancer Genomics
- * Systems Biology
Background:
- * The CIC gene encodes a transcriptional repressor and MAPK signaling effector, frequently inactivated in cancers, suggesting a tumor suppressor role.
- * Understanding CIC's functional network is crucial for elucidating its role in tumorigenesis.
Purpose of the Study:
- * To investigate the interaction networks of CIC using multi-omic approaches.
- * To characterize the functional consequences of CIC loss in cellular processes like cell cycle regulation and RNA splicing.
Main Methods:
- * Bioinformatic, genomic, and proteomic analyses to identify CIC interaction partners.
- * Examination of mitotic defects and gene expression in CIC-deficient cell lines and a mouse model.
- * Analysis of RNA splicing patterns in CIC-deficient cells.
Main Results:
- * Identified novel interactions between CIC and SWI/SNF complex members, cell cycle regulators, and RNA processing factors.
- * CIC loss correlates with increased mitotic defects and dysregulated mitotic regulators.
- * Aberrant RNA splicing, particularly in untranslated regions, was observed in CIC-deficient cells, affecting key cancer-related genes.
Conclusions:
- * CIC loss impacts cell cycle regulation, mitotic integrity, and RNA splicing, expanding its known functions.
- * Multi-omic network analysis effectively uncovers the complex roles of pleiotropic genes like CIC.
- * This research deepens the understanding of CIC's tumor suppressor functions and potential therapeutic strategies in cancer.
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