ALKBH5-mediated m6A demethylation of TXNDC5 drives malignant progression in gastric cancer

Nov 11, 2025Epigenomics

How a specific chemical change controlled by ALKBH5 on TXNDC5 helps stomach cancer grow

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Abstract

was significantly upregulated in gastric cancer tissues and cells.

Overexpression of ALKBH5 stabilized expression in a way dependent on .
Increased m6A methylation of TXNDC5 due to ALKBH5 knockdown led to reduced TXNDC5 protein expression.
Suppression of ALKBH5 resulted in decreased proliferation, migration, and invasion of gastric cancer cells.
In vivo studies indicated that loss of ALKBH5 impaired tumor growth.

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BACKGROUND: Gastric cancer (GC) remains a leading cause of cancer-related mortality worldwide. N6-methyladenosine (m6A) modification plays a critical role in post-transcriptional gene regulation. This study aimed to elucidate the molecular mechanism by which the RNA demethylase regulates GC progression through of thioredoxin domain-containing protein 5 ().

METHODS: Differential expression models of ALKBH5 and TXNDC5 were established in GC cells using RNA interference and gene overexpression. Methylated RNA immunoprecipitation (MeRIP-qPCR), qPCR, and Western blot were performed to assess ALKBH5-mediated m6A modification and its effect on TXNDC5 expression. Functional assays, including proliferation, migration, and invasion, as well as a xenograft mouse model, were used to evaluate their roles in GC progression.

RESULTS: ALKBH5 was significantly upregulated in GC tissues and cells. Overexpression of ALKBH5 stabilized TXNDC5 expression in an m6A-dependent manner, thereby promoting malignant phenotypes. Conversely, ALKBH5 knockdown increased m6A methylation of TXNDC5, reduced TXNDC5 protein expression, and suppressed GC cell proliferation, migration, and invasion. In vivo experiments confirmed that loss of ALKBH5 impaired tumor growth.

CONCLUSIONS: Our findings demonstrate that the ALKBH5-TXNDC5 axis drives GC progression through m6A-dependent regulation, highlighting ALKBH5 as a potential therapeutic target for GC.

Key numbers

410 of 450

Increase in expression

Gastric cancer samples show higher expression compared to normal tissues.

≥95%

Decrease in tumor growth

knockdown in xenograft models resulted in reduced tumor growth.

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ALKBH5-mediated m6A demethylation of TXNDC5 drives malignant progression in gastric cancer

Abstract

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