Hong Leyu, Ni Ming, Xue Fei, Jiang Tao, Wu Xuanpeng, Li Chenxi, Liang Shuhao, Chen Tianhao, Luo Chao, Wu Qifei
Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Yan Ta West Road No.277, Xi'an, 710061, Shaanxi, China.
Key Laboratory of Surgical Critical Care and Life Support (Xi'an Jiaotong University), Ministry of Education, Xi'an, China.
Lung. 2025 Mar 17;203(1):47. doi: 10.1007/s00408-025-00798-3.
Histone deacetylases (HDACs), a class of enzymes involved in epigenetic modifications, play a pivotal role in modulating chromatin structure and gene expression. Among these, histone deacetylase 3 (HDAC3) has emerged as a key regulator in diverse cellular pathophysiological processes. The remarkable therapeutic potential of HDAC inhibitors in lung cancer has intensified research into the role of HDAC3 in pulmonary diseases. Through deacetylating histones and non-histone proteins, HDAC3 has been increasingly recognized for its critical involvement in regulating inflammatory responses, fibrotic processes, and oncogenic signaling pathways, positioning it as a compelling therapeutic target. This review systematically examines the structural and functional features of HDAC3 and discusses its multifaceted contributions to pulmonary pathologies, including lung injury, pulmonary fibrosis, and lung cancer. Additionally, we critically evaluate advances in HDAC inhibitor-based therapies for lung cancer, with emphasis on the development of HDAC3-targeted therapies. As a promising therapeutic target for pulmonary diseases, HDAC3 needs to be further investigated to elucidate its regulatory mechanisms and facilitate the development of selective inhibitors for clinical translation.
组蛋白去乙酰化酶(HDACs)是一类参与表观遗传修饰的酶,在调节染色质结构和基因表达中起关键作用。其中,组蛋白去乙酰化酶3(HDAC3)已成为多种细胞病理生理过程中的关键调节因子。HDAC抑制剂在肺癌中显著的治疗潜力,强化了对HDAC3在肺部疾病中作用的研究。通过使组蛋白和非组蛋白去乙酰化,HDAC3因其在调节炎症反应、纤维化过程和致癌信号通路中的关键作用而越来越受到认可,使其成为一个引人注目的治疗靶点。本综述系统地研究了HDAC3的结构和功能特征,并讨论了其对肺部病理的多方面贡献,包括肺损伤、肺纤维化和肺癌。此外,我们批判性地评估了基于HDAC抑制剂的肺癌治疗进展,重点是HDAC3靶向治疗的发展。作为肺部疾病有前景的治疗靶点,HDAC3需要进一步研究以阐明其调节机制,并促进用于临床转化的选择性抑制剂的开发。