Histone Modification Networks Reshape the Metabolism and Treatment Landscape of Urological Cancers

作者：Fengye Liu, Longfei He, Muying Yu, Junyi Chen, Yuxiao Huang, Wenzhe Ma, Ying Wan, Bingru Zhou · 发表于：Frontiers in Bioscience-Landmark · 年份：2025 · DOI：10.31083/fbl42831 · 被引用次数：4 · 研究领域：Epigenetics and DNA Methylation、Histone Deacetylase Inhibitors Research、Cancer-related gene regulation

Histone post-translational modifications (HPTMs) have emerged as crucial epigenetic regulators in urological malignancies, including prostate, bladder, and renal cell carcinomas. This review systematically examines four key modifications-lactylation, acetylation, methylation, and phosphorylation-and their roles in carcinogenesis. These dynamic modifications, mediated by "writers", "erasers", and "readers", influence chromatin structure and gene expression, thereby driving oncogenic processes such as metabolic reprogramming, immune evasion, and treatment resistance. The newly discovered lactylation modification links cellular metabolism to epigenetic regulation through lactate-derived histone marks, particularly in clear cell renal cell carcinoma, where it activates oncogenic pathways. Acetylation modifications, regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs), modulate chromatin accessibility and are implicated in silencing cancer suppressors. Methylation patterns, controlled by histone lysine methyltransferases (KMTs) and histone lysine demethylases (KDMs), demonstrate dual roles in gene regulation, with specific marks either promoting or suppressing carcinogenesis. Finally, phosphorylation dynamics affect critical cellular processes such as cell cycle progression and DNA repair. This review underscores the therapeutic potential of targeting these modifications, as evidenced by promising results with HDAC and Enhancer of zeste homolog 2 (EZH2) ...