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A Systems-Level Analysis Reveals Circadian Regulation of Splicing in Colorectal Cancer

Rukeia El-Athman1, Luise Fuhr1, Angela Relógio1

  • 1Institute for Theoretical Biology (ITB), Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Germany; Medical Department of Hematology, Oncology, and Tumor Immunology, Molekulares Krebsforschungszentrum (MKFZ), Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Germany.

Ebiomedicine
|June 25, 2018
PubMed

Insights

The circadian clock influences gene splicing, impacting cancer progression. This study reveals how circadian rhythms and splicing interact in colon cancer cells, affecting metastasis.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Chronobiology

Background:

  • The circadian clock regulates numerous biological processes, and its dysregulation is linked to diseases like cancer.
  • Aberrant pre-messenger RNA (pre-mRNA) splicing is also a hallmark of many cancers.
  • Understanding the interplay between circadian rhythms and splicing is crucial for cancer research.

Purpose of the Study:

  • To investigate the role of the circadian clock in regulating pre-mRNA splicing within a cancer progression model.
  • To perform a systems-level, genome-wide analysis comparing rhythmic transcriptional profiles in primary and metastatic colon cancer cells.

Main Methods:

  • Genome-wide analysis of colon carcinoma cell lines (SW480 and SW620) from primary and metastatic sites.
  • Comparison of rhythmic transcriptional profiles to identify cell-specific circadian expression patterns.
  • Analysis of alternative splicing events and their circadian patterns in key genes.

Main Results:

  • Identified cell-specific circadian expression of spliceosome components and splicing factors (e.g., SRSF1, HNRNPLL, ESRP1, RBM 8A).
  • Detected altered alternative splicing events and circadian splicing patterns in cancer progression.
  • Observed changes in the splicing of genes critical for cancer, such as VEGFA, NCAM1, FGFR2, and CD44.

Conclusions:

  • Demonstrated a significant interplay between the circadian clock and pre-mRNA splicing in colon cancer.
  • These findings suggest potential roles for circadian-regulated splicing in tumor progression and metastasis.
  • Highlights the importance of considering circadian biology in cancer research and therapeutic strategies.
Keywords:
Alternative splicingCircadian clockColorectal cancer progressionDifferential rhythmicitySpliceosomeSplicing factors

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