PHF5A, also known as PHD-finger domain protein 5A, is a highly conserved protein with 110 amino acids, belonging to PHD zinc finger proteins. It is an essential component of the SF3B splicing complex, regulating protein-protein or protein-DNA interactions, especially 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].

In cancer research, PHF5A has been shown to play significant roles. In colorectal cancer, its acetylation at lysine 29 in response to cellular stresses, dependent on p300, affects global pre-mRNA splicing, upregulates KDM3A through alternative splicing, and contributes to carcinogenesis and stress resistance of cancer cells [1]. PHF5A is frequently upregulated in colorectal cancer samples, promoting cell proliferation and metastasis by inducing TEAD2 exon 2 inclusion to activate YAP signaling [3]. In esophageal squamous cell carcinoma, it is highly expressed, promoting cell proliferation, migration, and inhibiting apoptosis by stabilizing VEGFA [4]. In head and neck squamous cell carcinoma, it regulates the alternative splicing of DOCK5 to promote cancer progression through p38 MAPK activation [5]. In gastric cancer, it facilitates cancer development through SKP2-mediated stabilization of FOS [6].

In conclusion, PHF5A is crucial for pre-mRNA splicing and various cellular processes. Its dysregulation in multiple cancers, as revealed by in-vivo and functional studies, suggests its potential as a diagnostic, prognostic, and therapeutic target in cancer treatment. Research on PHF5A using gene knockout or conditional knockout mouse models could further clarify its role in normal and disease-related biological processes, especially in cancer [2,3,4,5,6].