Role of CHD4 in tumor progression, DNA damage response and treatment resistance (Review)

Chromodomain helicase DNA‑binding protein 4 (CHD4) is a core adenosine triphosphate (ATP)‑dependent chromatin‑remodeling factor of the nucleosome‑remodeling and deacetylase (NuRD) complex. It plays a crucial role in chromatin structure regulation, gene expression regulation, and DNA damage response. It has been demonstrated that CHD4 has context‑dependent functions in tumor development and progression. It can influence tumor progression via such mechanisms as regulating tumor‑related signaling pathways, maintaining the silencing of tumor suppressor genes, and promoting metabolic adaptation; it can also exert tumor‑suppressive effects in specific transcriptional regulatory environments. Additionally, during DNA damage response, CHD4 participates in chromatin remodeling at damage sites, in cell cycle recovery, and in repair pathway selection. It is also involved in the development of tumor treatment resistance through mechanisms that include regulation of DNA repair, cell cycle progression, drug efflux, the tumor immune microenvironment, and replication fork stability. It has also been shown that various non‑coding RNAs participate in the functional regulation of CHD4 by modulating its expression, localization, and protein stability. In summary, as a key node connecting chromatin regulation, genome stability, and tumor treatment response, CHD4 holds significant importance in tumor progression and treatment.