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Updated: Oct 25, 2025

Deficient Pms2, ERCC1, Ku86, CcOI in Field Defects During Progression to Colon Cancer
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Deficient Pms2, ERCC1, Ku86, CcOI in Field Defects During Progression to Colon Cancer

Published on: July 28, 2010

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CDX2 inducible microRNAs sustain colon cancer by targeting multiple DNA damage response pathway factors

Swati Priya1, Ekjot Kaur1, Swati Kulshrestha1

  • 1Signal Transduction Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.

Journal of Cell Science
|August 9, 2021
PubMed

Insights

Researchers identified DNA damage sensitive miRs (DDSMs) in colon cancer. These DDSMs, regulated by CDX2, impact DNA damage response (DDR) and patient survival, offering potential as a prognostic biomarker.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Colon adenocarcinoma exhibits complex molecular alterations.
  • DNA damage response (DDR) pathways are crucial in cancer development.
  • MicroRNAs (miRs) play significant roles in gene regulation and cancer.

Purpose of the Study:

  • To identify and characterize microRNA signatures responsive to DNA damage in colon cancer.
  • To elucidate the regulatory mechanisms of these microRNAs.
  • To evaluate their potential as prognostic biomarkers for colon cancer.

Main Methods:

  • Meta-analysis of colon adenocarcinoma patient tissue transcriptomes.
  • Experimental validation in independent patient cohorts and cellular models.
  • Analysis of transcription factor (CDX2) and epigenetic modifier (HDAC1/2) interactions.
  • Assessment of microRNA target genes within the DDR pathway.
  • Correlation analysis with clinical data, including survival probability.

Main Results:

  • Identification of a DNA damage sensitive miR (DDSM) signature.
  • DDSMs are transcriptionally upregulated by CDX2 and repressed by HDAC1/2 complexes.
  • DDSMs downregulate key DDR genes like BRCA1, ATM, CHEK1, and RNF8.
  • CDX2-regulated DDSMs promote tumor growth and metastasis in preclinical models.
  • DDSMs negatively correlate with BRCA1 and patient survival in colon cancer.

Conclusions:

  • A novel DDSM signature regulated by CDX2 is identified in colon cancer.
  • This DDSM signature plays a role in modulating the DNA damage response.
  • DDSMs serve as potential prognostic biomarkers for colon cancer patients.
Keywords:
ATMBLMBRCA1Chk1Colon cancerDNA damage responseDNA repairRNF8microRNA

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