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Updated: Feb 1, 2026

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Cadmium-induced POLN mutations promote m6A-dependent circ_FANCA degradation via endoribonucleolytic cleavage,

Hongyu Hao1, Wenyu Wang1, Yanshu Li2

  • 1School of Public Health, Baotou Medical College, Baotou 014030, China.

Journal of Hazardous Materials
|January 30, 2026
PubMed

Insights

Cadmium exposure causes cancer by mutating DNA polymerase Nu (POLN), leading to circ_FANCA loss. This disrupts cellular metabolism, promoting tumor growth and malignant transformation.

Area of Science:

  • Environmental Toxicology
  • Molecular Biology
  • Cancer Research

Background:

  • Cadmium (Cd) is a carcinogenic heavy metal.
  • Genetic and epigenetic changes contribute to Cd-induced cancer.
  • The interplay between genetic and epigenetic mechanisms in Cd carcinogenesis is unclear.

Purpose of the Study:

  • To investigate a novel pathway linking Cd exposure to metabolic reprogramming.
  • To elucidate the role of genetic and epitranscriptomic dysregulation in Cd-induced carcinogenesis.
  • To understand the crosstalk between genetic mutations and epitranscriptomic modifications.

Main Methods:

  • Utilized a Cd-induced cellular malignant transformation model.
  • Performed integrated genomic and transcriptomic analyses.
  • Conducted mechanistic studies on gene mutations, circRNA decay, and metabolic pathways.

Main Results:

  • Cadmium exposure induced mutagenesis in DNA polymerase Nu (POLN).
  • POLN mutations led to circ_FANCA downregulation, enhancing malignant transformation.
  • Mutated POLN recognized m6A-modified circ_FANCA, recruiting an endonuclease complex to accelerate circRNA decay.
  • Loss of tumor suppressor circ_FANCA resulted in tricarboxylic acid (TCA) cycle hyperactivation, promoting oncogenesis.

Conclusions:

  • A novel pathway links Cd exposure to metabolic reprogramming via genetic (POLN mutation) and epitranscriptomic (circ_FANCA dysregulation) mechanisms.
  • This pathway involves accelerated circRNA decay and TCA cycle hyperactivation, creating a pro-oncogenic metabolic environment.
  • Findings provide a new mechanistic framework for understanding chemical carcinogenesis by cadmium.
Keywords:
CadmiumCirc_FANCAMalignant transformationPOLN mutationTCA cycle

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