International journal of biological macromoleculesOct 1, 2025

ALKBH5's complex role in controlling cancer cell iron-related death

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 28, 2026

Abstract

ALKBH5 is associated with both pro-tumorigenic and anti-tumorigenic roles in cancer.

N-methyladenosine (mA) modification influences RNA metabolism through the action of Writers, Erasers, and Readers.
ALKBH5 is a key mA demethylase that can impact mRNA stability, translation, and splicing.
Ferroptosis, a type of cell death linked to iron and lipid peroxides, may affect tumor progression and treatment resistance.
ALKBH5 regulates ferroptosis pathways, suggesting a complex role in cancer development.
The review highlights the context-dependent functions of ALKBH5 in both promoting and suppressing tumors.

Simplified

N-methyladenosine (mA) modification, a pivotal epitranscriptomic mechanism regulating RNA metabolism, is dynamically orchestrated by methyltransferases (Writers), demethylases (Erasers), and binding proteins (Readers). ALKBH5, a core mA demethylase, manifests a dual role, either pro-tumorigenic or anti-tumorigenic, in cancers by modulating mRNA stability, translation, and splicing of target genes. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxide accumulation, is intimately linked to tumor progression and therapy resistance. Emerging evidence reveals that ALKBH5 functions as a "double-edged sword" in cancers by critically regulating ferroptosis pathways. This review systematically elucidates the complex, context-dependent duality of ALKBH5 in modulating ferroptosis during cancer development, dissecting its tumor-suppressive and tumor-promoting mechanisms across diverse malignancies. 6 6 6

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ALKBH5's complex role in controlling cancer cell iron-related death

Abstract

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