Cancer lettersJan 6, 2025

ALKBH5 may help brain tumor growth through a specific RNA modification process in glioma

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 3, 2026

Abstract

ALKBH5 expression was dramatically increased in glioma and predicted poor prognosis.

High levels of ALKBH5 are associated with enhanced cell proliferation, migration, and invasion in glioma.
In vivo studies indicate that overexpression of ALKBH5 accelerates tumor growth.
ALKBH5 may act by demethylating FOXO1 mRNA, leading to reduced stability and expression of FOXO1.
The downregulation of FOXO1 is linked to increased nuclear accumulation of β-catenin, activating oncogenic Wnt/β-catenin signaling.
Targeting the ALKBH5/FOXO1 axis could offer a new therapeutic approach for treating glioma.

Simplified

N-methyladenosine (m6A) methylation, is a well-known epigenetic modification involved in various biological processes, including tumorigenesis. However, the role of AlkB homolog 5 (ALKBH5), a critical component of m6A modification, remains unclear in glioma. This study investigates the function of ALKBH5 in glioma progression and its potential as a therapeutic target. We found that ALKBH5 expression was dramatically increased in glioma, and high expression of ALKBH5 predicted poor prognosis. Overexpression of ALKBH5 promotes cell proliferation, migration, and invasion in vitro and accelerates tumor growth in vivo. Furthermore, m6A-MeRIP-seq, MeRIP-qPCR, RNA pulldown, and immunoprecipitation assays revealed that the transcription factor, forkhead box protein O1 (FOXO1), was the potential target of ALKBH5. Mechanistically, ALKBH5 facilitates glioma progression by demethylating m6A-modified FOXO1 mRNA, thereby destroying FOXO1 stability and expression through a YTHDC1-dependent pathway. The downregulated FOXO1 interacts with β-catenin, increasing its nuclear accumulation and thus promoting oncogenic Wnt/β-catenin signaling. Our findings suggest that targeting the ALKBH5/FOXO1 axis may provide a novel therapeutic strategy for glioma treatment. 6

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Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

PubMed

ALKBH5 may help brain tumor growth through a specific RNA modification process in glioma

Abstract

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Competing interests

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Abstract

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