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<p>Aldo-keto reductase 1B10 (AKR1B10), a prominent member of the human aldo-keto reductase superfamily, plays dual roles in maintaining physiological homeostasis and participating in pathological processes. Beyond its established functions in carbohydrate metabolism, lipid metabolism, and oxidative stress regulation, AKR1B10 has been demonstrated as a critical mediator of tumor cell proliferation and metastasis. Compelling evidence reveals tumor-specific overexpression of AKR1B10 in multiple malignancies, including hepatocellular carcinoma (HCC), lung cancer, and breast cancer, contrasting sharply with its minimal expression in normal tissues. The enzyme’s remarkable tumor selectivity and its emerging potential as a serum biomarker further underscore its clinical significance. Elucidating the comprehensive regulatory network governing AKR1B10 expression and function is paramount for understanding disease mechanisms and developing targeted therapies. This review systematically examines the structural characteristics of the AKR1B10 protein and its promoter region, and delineates its multidimensional upstream regulatory network encompassing transcription factors, epigenetic modifications, and environmental stimuli. To highlight the central role of AKR1B10 in disease, we provide an integrative discussion on the crosstalk among three pivotal pathways: metabolic regulation, oxidative stress response, and proliferation/invasion signaling, specifically highlighting three dynamic feedback loops that maintain tumor homeostasis: the Nrf2-redox survival loop, the ERK-c-Jun signaling self-limiting loop, and the Wnt/β-catenin context-dependent loop. Furthermore, specific emphasis is placed on HCC, addressing its lipid metabolic dependency, the chronic inflammatory/oxidative milieu, and the detectability of secretory AKR1B10, as well as the current status and challenges of therapeutic interventions. Although the current understanding of the intricate interplay between AKR1B10 and its regulatory components remains incomplete, they collectively constitute a sophisticated signaling network. By synthesizing existing knowledge, this review constructs a “structure-function” framework and regulatory landscape of AKR1B10, aiming to offer valuable insights for the future development of therapeutic strategies targeting AKR1B10-associated pathways.</p>

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The pathway network of aldo-keto reductase 1b10: a new perspective on gene-targeted therapy

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月22日

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  • Chen Wang,
  • Zhuang Xiong,
  • Xiang Wang,
  • Jing Liang,
  • Haoyang Li,
  • Siqi He,
  • Chengkun Wang,
  • Yang Zhang

摘要

Aldo-keto reductase 1B10 (AKR1B10), a prominent member of the human aldo-keto reductase superfamily, plays dual roles in maintaining physiological homeostasis and participating in pathological processes. Beyond its established functions in carbohydrate metabolism, lipid metabolism, and oxidative stress regulation, AKR1B10 has been demonstrated as a critical mediator of tumor cell proliferation and metastasis. Compelling evidence reveals tumor-specific overexpression of AKR1B10 in multiple malignancies, including hepatocellular carcinoma (HCC), lung cancer, and breast cancer, contrasting sharply with its minimal expression in normal tissues. The enzyme’s remarkable tumor selectivity and its emerging potential as a serum biomarker further underscore its clinical significance. Elucidating the comprehensive regulatory network governing AKR1B10 expression and function is paramount for understanding disease mechanisms and developing targeted therapies. This review systematically examines the structural characteristics of the AKR1B10 protein and its promoter region, and delineates its multidimensional upstream regulatory network encompassing transcription factors, epigenetic modifications, and environmental stimuli. To highlight the central role of AKR1B10 in disease, we provide an integrative discussion on the crosstalk among three pivotal pathways: metabolic regulation, oxidative stress response, and proliferation/invasion signaling, specifically highlighting three dynamic feedback loops that maintain tumor homeostasis: the Nrf2-redox survival loop, the ERK-c-Jun signaling self-limiting loop, and the Wnt/β-catenin context-dependent loop. Furthermore, specific emphasis is placed on HCC, addressing its lipid metabolic dependency, the chronic inflammatory/oxidative milieu, and the detectability of secretory AKR1B10, as well as the current status and challenges of therapeutic interventions. Although the current understanding of the intricate interplay between AKR1B10 and its regulatory components remains incomplete, they collectively constitute a sophisticated signaling network. By synthesizing existing knowledge, this review constructs a “structure-function” framework and regulatory landscape of AKR1B10, aiming to offer valuable insights for the future development of therapeutic strategies targeting AKR1B10-associated pathways.