The Role of HDAC3 in Pulmonary Diseases

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.