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.

Cancers
|June 22, 2023
PubMed

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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