PHF5A, also known as PHD-finger domain protein 5A, is a highly conserved protein with 110 amino acids, belonging to PHD zinc finger proteins and ubiquitously expressed in eukaryotic nuclei [2]. It is an essential component of the SF3B splicing complex, regulating protein-protein or protein-DNA interactions and playing a key role in pre-mRNA splicing. Besides its splicing-related functions, PHF5A is also involved in cell cycle regulation, morphological development, DNA damage repair, maintenance of pluripotent embryonic stem cells, embryogenesis, and regulation of chromatin-mediated transcription [2].

PHF5A has been implicated in multiple cancer-related processes. In colorectal cancer, its acetylation at lysine 29 under stress strengthens U2 snRNPs interaction, affects pre-mRNA splicing, stabilizes KDM3A mRNA, and promotes protein expression, correlating with poor prognosis [1]. In esophageal squamous cell carcinoma, high PHF5A expression promotes tumor progression by stabilizing VEGFA [3]. In head and neck squamous cell carcinoma, it regulates the alternative splicing of DOCK5 to promote tumor progression through p38 MAPK activation [4]. In gastric cancer, knockdown of PHF5A inhibits tumor progression through SKP2-mediated ubiquitination of FOS [5].

In conclusion, PHF5A is crucial for pre-mRNA splicing and various cellular processes. Its dysregulation is associated with the development and progression of multiple cancers, such as colorectal, esophageal, head and neck, and gastric cancers. Studies on PHF5A, including those using loss-of-function models, help in understanding its role in cancer biology, potentially providing new therapeutic targets for cancer treatment.