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Genome-wide profiling of chemoradiation‑induced changes in alternative splicing in colon cancer cells

Wei Xiong1, Depei Gao2, Yunfeng Li3

  • 1Department of Radiation Oncology, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650118, P.R. China.

Oncology Reports
|August 31, 2016
PubMed

Insights

Alternative splicing, a key regulator of protein diversity, plays a role in chemoradiation-resistant colon cancer. Exon skipping significantly increased in resistant cells, impacting DNA replication and repair pathways.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genomics

Background:

  • Alternative splicing regulates protein diversity and is linked to colon cancer progression.
  • The role of alternative splicing in chemoradiation-resistant colon cancer is not well understood.

Purpose of the Study:

  • To investigate the function of alternative splicing in chemoradiation-resistant colon cancer.
  • To identify differences in gene expression and splicing between normal and resistant colon cancer cells.

Main Methods:

  • Construction of a chemoradiation-resistant colon cancer cell line (RCR-HCT116).
  • RNA-sequencing to compare gene expression between normal (HCT116) and RCR-HCT116 cells.
  • Gene Ontology (GO) analysis and alternative splicing event analysis.

Main Results:

  • Identified 818 highly expressed genes in normal HCT116 cells (cell cycle, division) and 285 in RCR-HCT116 cells (system processes, response to wounding).
  • Exon skipping was significantly increased in chemoradiation-resistant colon cancer cells.
  • 323 differential alternative splicing events in 293 genes were identified, functionally related to DNA replication, DNA damage response, and helicase activity.

Conclusions:

  • Alternative splicing, particularly exon skipping, is altered in chemoradiation-resistant colon cancer.
  • These alterations affect genes involved in critical processes like DNA replication and repair.
  • Findings provide insights into the molecular mechanisms underlying chemoradiation resistance in colon cancer.

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