ALKBH5-Mediated ITGB1 m6A Modification in Ovarian Cancer Progression and Immune Evasion

Ovarian cancer (OC) is the deadliest gynecologic malignancy, with immune evasion contributing to its poor prognosis. This study reveals that the m6A demethylase ALKBH5 enhances OC progression and immune escape by regulating ITGB1 expression. Using bulk and single-cell RNA sequencing, deep learning, and co-expression network analysis, we identified ALKBH5 as a key regulator of m6A-modified ITGB1. Functional experiments showed that ALKBH5 promotes OC cell proliferation, metastasis, and immune evasion, while its knockdown enhances T cell-mediated cytotoxicity. Public database validation further confirmed the diagnostic value of ALKBH5 and ITGB1. Mechanistically, ALKBH5 binds to ITGB1 mRNA and removes m6A modifications, increasing its stability and expression. Targeting the ALKBH5-ITGB1 axis may offer novel diagnostic biomarkers and therapeutic strategies for OC.

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Publication Details

Journal
npj Precision Oncology
Published
2025-12-09
DOI
https://doi.org/10.1038/s41698-025-01127-w
Primary Topic
RNA modifications and cancer
Type
article
Field-Weighted Citation Impact
0.00
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article

ALKBH5-Mediated ITGB1 m6A Modification in Ovarian Cancer Progression and Immune Evasion

Cheng Du, Dalu Wang, Zheng He, Mingyue Ma et al.
npj Precision Oncology
RNA modifications and cancer
article

ALKBH5-Mediated ITGB1 m6A Modification in Ovarian Cancer Progression and Immune Evasion

Cheng Du, Dalu Wang, Zheng He, Mingyue Ma, Weijia Zhao
article en

Abstract

Ovarian cancer (OC) is the deadliest gynecologic malignancy, with immune evasion contributing to its poor prognosis. This study reveals that the m6A demethylase ALKBH5 enhances OC progression and immune escape by regulating ITGB1 expression. Using bulk and single-cell RNA sequencing, deep learning, and co-expression network analysis, we identified ALKBH5 as a key regulator of m6A-modified ITGB1. Functional experiments showed that ALKBH5 promotes OC cell proliferation, metastasis, and immune evasion, while its knockdown enhances T cell-mediated cytotoxicity. Public database validation further confirmed the diagnostic value of ALKBH5 and ITGB1. Mechanistically, ALKBH5 binds to ITGB1 mRNA and removes m6A modifications, increasing its stability and expression. Targeting the ALKBH5-ITGB1 axis may offer novel diagnostic biomarkers and therapeutic strategies for OC.

npj Precision OncologyVol. 9(1)
China Medical University (CN)
Openalex Percentile: Top 64%
RNA modifications and cancer
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