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Epigenetically inhibiting CYP3A5 modulates the migration and invasion of esophageal squamous cell carcinoma

Xintong Jiang1, Yanhong Wang2, Jun Ouyang3

  • 1Institute of Drug Metabolism and Pharmaceutical Analysis, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.

Drug Metabolism and Disposition: the Biological Fate of Chemicals
|November 28, 2025
PubMed

Insights

CYP3A5 expression is reduced in esophageal squamous cell carcinoma (ESCC), promoting tumor metastasis. Restoring CYP3A5 levels may offer a new therapeutic strategy for ESCC treatment and prevention.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Esophageal squamous cell carcinoma (ESCC) presents a significant global health challenge with high mortality.
  • Aberrant suppression of the CYP3A5 gene is a common observation in ESCC, but its role and regulatory mechanisms are not fully understood.

Purpose of the Study:

  • To investigate the function of CYP3A5 in ESCC.
  • To elucidate the epigenetic mechanisms underlying CYP3A5 transcriptional repression in ESCC.
  • To evaluate CYP3A5 as a potential biomarker and therapeutic target for ESCC.

Main Methods:

  • Comparative analysis of CYP3A5 expression in ESCC tumor versus normal tissues.
  • Assessment of the correlation between CYP3A5 expression and patient prognosis/metastasis.
  • Treatment with histone deacetylase inhibitor (trichostatin A) to observe effects on CYP3A5 expression.
  • Mechanistic studies involving histone deacetylase 4 (HDAC4), H3K18/K27 acetylation, and the CYP3A5 promoter.
  • In vitro and in vivo experiments to assess the functional impact of CYP3A5 overexpression on ESCC cell migration and invasion.

Main Results:

  • CYP3A5 expression is significantly decreased in ESCC tissues.
  • Higher CYP3A5 expression correlates with improved prognosis and reduced tumor metastasis.
  • Histone deacetylase 4 (HDAC4) mediates the suppression of CYP3A5 via reduced histone acetylation at its promoter.
  • Overexpression of CYP3A5 inhibits ESCC cell migration and invasion.

Conclusions:

  • CYP3A5 plays a critical role in suppressing tumor metastasis and invasion in ESCC.
  • Epigenetic repression of CYP3A5 by HDAC4 contributes to ESCC progression.
  • CYP3A5 represents a promising biomarker and therapeutic target for preventing metastasis in ESCC.
Keywords:
CYP3A5Esophageal squamous cell carcinomaHistone acetylationMetastasis

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