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2000
Volume 26, Issue 5
  • ISSN: 1389-2002
  • E-ISSN: 1875-5453

Abstract

Introduction

CYP1B1, a crucial drug-metabolizing enzyme, metabolizes both endogenous compounds and clinical drugs. The present study investigated the effects of CYP1B1 on the proliferation, migration, apoptosis, and ferroptosis of HCC cells. It further elucidated the regulatory role of m6A modification particularly the methyltransferase METTL14 in regulating CYP1B1 mRNA stability and translation efficiency.

Methods

CCK-8, colony formation, wound healing, and transwell assays were employed to assess the role of CYP1B1 in HCC cell proliferation and migration. Ferroptosis-related assays, Western blot analysis, RNA immunoprecipitation, and RNA stability assays were conducted to elucidate the underlying molecular mechanisms. The Hepatocellular Carcinoma Database (HCCDB) was utilized for gene expression analysis of CYP1B1 and METTL14.

Results

Upregulated CYP1B1 in HCC inhibits ferroptosis and promotes cell proliferation by mediating GPX4, without significantly affecting HCC cell migration or apoptosis. METTL14-mediated m6A modification negatively regulates CYP1B1 expression in HCC. Specifically, METTL14 (downregulated in HCC) catalyzes m6A methylation of CYP1B1 mRNA, reducing its stability, while YTHDF3 binds to CYP1B1 mRNA to decrease its expression.

Discussion

These findings established a functional link between drug metabolism, m6A epigenetics, and iron-dependent cell death in HCC, highlighting CYP1B1 and its upstream m6A machinery as potential targets for developing precision therapies that enhance ferroptosis sensitivity in HCC. The clinical relevance of the identified molecular mechanisms necessitates additional in-depth exploration.

Conclusion

CYP1B1 promotes HCC cell proliferation by regulating GPX4-mediated ferroptosis resistance, while METTL14-mediated m6A modification serves as a key negative regulatory mechanism for CYP1B1. Targeting CYP1B1 as a therapeutic strategy holds substantial promise for future drug development in HCC.

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2025-08-13
2026-02-02

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m6A Modified-CYP1B1 Promotes HCC Cell Proliferation by Inhibiting Ferroptosis
Current Drug Metabolism 26, 330 (2025); https://doi.org/10.2174/0113892002387502250714112923
/content/journals/cdm/10.2174/0113892002387502250714112923
/content/journals/cdm/10.2174/0113892002387502250714112923
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  • Article Type:     Research Article
Keyword(s): CYP1B1; drug-metabolizing; ferroptosis; HCC; m6A; machinery

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