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The methylation-expression correlation of autophagy-related genes in colorectal cancer patients from southern Iran

  • 0Autophagy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Molecular Biology Research Communications +

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September 15, 2025

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September 15, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Investigating epigenetic modifications in colorectal cancer (CRC), this study found that promoter hypermethylation of autophagy-associated genes (ATGs) paradoxically correlated with increased gene expression in most CRC patients. This suggests complex regulatory mechanisms in CRC.

Area Of Science

  • Molecular biology
  • Cancer research
  • Epigenetics

Background

  • Colorectal cancer (CRC) presents a significant global health challenge due to high mortality and rising morbidity.
  • The autophagy pathway is integral to CRC development and therapeutic resistance.
  • Epigenetic modifications, particularly DNA methylation, are key regulators of gene expression in cancer.

Purpose Of The Study

  • To examine the effect of promoter methylation on the expression of specific autophagy-associated genes (ATGs): ATG2B, ATG4D, ATG9A, and ATG9B.
  • To investigate the relationship between ATG gene methylation status and clinicopathological features in CRC patients.
  • To elucidate the complex interplay between epigenetic regulation and gene expression in CRC.

Main Methods

  • DNA and RNA extraction from CRC tissues and adjacent normal tissues.
  • Methylation-specific PCR (MSP) to assess gene promoter methylation status.
  • Quantitative real-time PCR (qRT-PCR) to determine mRNA expression levels of selected ATGs.

Main Results

  • Autophagy-associated genes (ATGs) exhibited significantly higher mRNA expression in CRC tissues compared to normal tissues across most patients.
  • No significant correlation was observed between the methylation status of ATG genes and the clinicopathological characteristics of CRC patients.
  • A notable finding was the frequent co-occurrence of promoter hypermethylation and high mRNA expression for ATG2B, ATG4D, ATG9A, and ATG9B in CRC tissues, contrary to typical gene silencing effects.

Conclusions

  • The study reveals a complex and potentially reversed association between promoter hypermethylation and gene expression for specific ATGs in CRC, suggesting that cancer type, stage, and compensatory mechanisms influence these epigenetic effects.
  • These findings underscore the intricate nature of epigenetic regulation of autophagy-associated genes in colorectal cancer.
  • Further extensive research is warranted to fully understand the role of ATG gene methylation in CRC pathogenesis and to identify potential diagnostic biomarkers or therapeutic targets.

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