Biological interpretation of DNA/RNA modification by ALKBH proteins and their role in human cancer

Abstract AlkB homolog (ALKBH) belongs to 2-oxoglutarate (2OG) and ferrous iron-dependent oxygenases, which can catalyze the demethylation of DNA/RNA and play an important role in human diseases represented by cancer. Although ALKBH has been extensively studied, the biological explanation for its spe...

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Main Authors: Siqi Yang, Jixiang Xing, Yancheng Song, Jiafu Cui, Lingling Bao, Qilemuge Xi, Yongchun Zuo
Format: Article
Language:English
Published: BMC 2025-06-01
Series:European Journal of Medical Research
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Online Access:https://doi.org/10.1186/s40001-025-02735-9
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author Siqi Yang
Jixiang Xing
Yancheng Song
Jiafu Cui
Lingling Bao
Qilemuge Xi
Yongchun Zuo
author_facet Siqi Yang
Jixiang Xing
Yancheng Song
Jiafu Cui
Lingling Bao
Qilemuge Xi
Yongchun Zuo
author_sort Siqi Yang
collection DOAJ
description Abstract AlkB homolog (ALKBH) belongs to 2-oxoglutarate (2OG) and ferrous iron-dependent oxygenases, which can catalyze the demethylation of DNA/RNA and play an important role in human diseases represented by cancer. Although ALKBH has been extensively studied, the biological explanation for its specific recognition of DNA/RNA and its mechanism of action in cancer remains unclear. This review explores the molecular mechanism of ALKBH protein binding to DNA/RNA through structural fitting and ChIP-Seq analysis and summarizes the structural biology factors that lead to its specific substrate recognition. Furthermore, the expression of ALKBH protein across different tissues is systematically compiled, with a tissue-specific expression map generated for 15 organs and 50 tissues. These maps provide valuable insights into the protein’s function in various physiological contexts. Additionally, this review systematically summarizes the regulatory role of the ALKBH protein in the occurrence and development of cancer. It highlights the protein’s involvement in key signaling pathways, including Wnt, AKT, AMPK, NF-κB, Hippo, and Notch, revealing its potential for application in early diagnosis and targeted cancer therapy. Overall, this review comprehensively expounds the biological functions of the ALKBH protein and its important role in cancer, which has important theoretical value and application prospects.
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spelling doaj-art-8d34e87edaae4211b30cd9de82b73bac2025-08-20T02:05:49ZengBMCEuropean Journal of Medical Research2047-783X2025-06-0130111110.1186/s40001-025-02735-9Biological interpretation of DNA/RNA modification by ALKBH proteins and their role in human cancerSiqi Yang0Jixiang Xing1Yancheng Song2Jiafu Cui3Lingling Bao4Qilemuge Xi5Yongchun Zuo6State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Institutes of Biomedical Sciences, College of Life Sciences, Inner Mongolia UniversityState Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Institutes of Biomedical Sciences, College of Life Sciences, Inner Mongolia UniversityState Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Institutes of Biomedical Sciences, College of Life Sciences, Inner Mongolia UniversityState Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Institutes of Biomedical Sciences, College of Life Sciences, Inner Mongolia UniversityState Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Institutes of Biomedical Sciences, College of Life Sciences, Inner Mongolia UniversityState Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Institutes of Biomedical Sciences, College of Life Sciences, Inner Mongolia UniversityState Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Institutes of Biomedical Sciences, College of Life Sciences, Inner Mongolia UniversityAbstract AlkB homolog (ALKBH) belongs to 2-oxoglutarate (2OG) and ferrous iron-dependent oxygenases, which can catalyze the demethylation of DNA/RNA and play an important role in human diseases represented by cancer. Although ALKBH has been extensively studied, the biological explanation for its specific recognition of DNA/RNA and its mechanism of action in cancer remains unclear. This review explores the molecular mechanism of ALKBH protein binding to DNA/RNA through structural fitting and ChIP-Seq analysis and summarizes the structural biology factors that lead to its specific substrate recognition. Furthermore, the expression of ALKBH protein across different tissues is systematically compiled, with a tissue-specific expression map generated for 15 organs and 50 tissues. These maps provide valuable insights into the protein’s function in various physiological contexts. Additionally, this review systematically summarizes the regulatory role of the ALKBH protein in the occurrence and development of cancer. It highlights the protein’s involvement in key signaling pathways, including Wnt, AKT, AMPK, NF-κB, Hippo, and Notch, revealing its potential for application in early diagnosis and targeted cancer therapy. Overall, this review comprehensively expounds the biological functions of the ALKBH protein and its important role in cancer, which has important theoretical value and application prospects.https://doi.org/10.1186/s40001-025-02735-9Structural topologyOmics analysisDNA/RNA recognitionTissue-specific expressionSignaling pathways
spellingShingle Siqi Yang
Jixiang Xing
Yancheng Song
Jiafu Cui
Lingling Bao
Qilemuge Xi
Yongchun Zuo
Biological interpretation of DNA/RNA modification by ALKBH proteins and their role in human cancer
European Journal of Medical Research
Structural topology
Omics analysis
DNA/RNA recognition
Tissue-specific expression
Signaling pathways
title Biological interpretation of DNA/RNA modification by ALKBH proteins and their role in human cancer
title_full Biological interpretation of DNA/RNA modification by ALKBH proteins and their role in human cancer
title_fullStr Biological interpretation of DNA/RNA modification by ALKBH proteins and their role in human cancer
title_full_unstemmed Biological interpretation of DNA/RNA modification by ALKBH proteins and their role in human cancer
title_short Biological interpretation of DNA/RNA modification by ALKBH proteins and their role in human cancer
title_sort biological interpretation of dna rna modification by alkbh proteins and their role in human cancer
topic Structural topology
Omics analysis
DNA/RNA recognition
Tissue-specific expression
Signaling pathways
url https://doi.org/10.1186/s40001-025-02735-9
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