REVIEW article
Front. Oncol.
Sec. Molecular and Cellular Oncology
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1562861
This article is part of the Research TopicLong Noncoding RNAs in CancerView all 3 articles
The Bidirectional Regulatory Network Between ATF4 and lncRNAs in Systemic Diseases
Provisionally accepted
- 1Yanshan University, Qinhuangdao, China
- 2Wenzhou Medical University, Wenzhou, Zhejiang Province, China
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Long non-coding RNAs (lncRNAs) are pivotal regulators of gene expression across multiple biological contexts, including stress responses and cellular adaptation. Activating transcription factor 4 (ATF4) is a key transcriptional effector of the integrated stress response (ISR), modulating genes involved in redox balance, amino acid metabolism, autophagy, and apoptosis. Emerging evidence has uncovered complex interactions between ATF4 and lncRNAs in systemic diseases, where lncRNAs can act as either downstream targets or upstream modulators of ATF4 signaling. This bidirectional crosstalk influences critical processes such as tumor progression, metabolic reprogramming, immune evasion, and skeletal homeostasis. In this review, we comprehensively summarize the regulatory roles of ATF4-lncRNA interactions in four major physiological systems: digestive, respiratory, immune, and skeletal. Furthermore, we highlight the therapeutic potential of selectively targeting these lncRNAs to modulate ATF4-mediated stress responses in a disease-and context-dependent manner. Our insights provide a conceptual framework and translational perspective for future research and precision therapies targeting the ATF4-lncRNA regulatory axis.
Keywords: lncRNA, ATF4, Systemic diseases, molecular targets, Human health
Received: 18 Jan 2025; Accepted: 11 Jul 2025.
Copyright: © 2025 Wu, Huang, Ma, Xuetong, Wu and Miao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Dongdong Wu, Yanshan University, Qinhuangdao, China
Zhang Miao, Yanshan University, Qinhuangdao, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.