Splicing control by PHF5A is crucial for melanoma cell survival
Tina Meißgeier , Melanie Kappelmann-Fenzl , Sebastian Staebler , Ata Jadid Ahari , Christian Mertes , Julien Gagneur , Lisa Linck-Paulus , Anja Katrin Bosserhoff
Cell Proliferation ›› 2025, Vol. 58 ›› Issue (2) : e13741
Splicing control by PHF5A is crucial for melanoma cell survival
Abnormalities in alternative splicing are a hallmark of cancer formation. In this study, we investigated the role of the splicing factor PHD finger protein 5A (PHF5A) in melanoma. Malignant melanoma is the deadliest form of skin cancer, and patients with a high PHF5A expression show poor overall survival. Our data revealed that an siRNA-mediated downregulation of PHF5A in different melanoma cell lines leads to massive splicing defects of different tumour-relevant genes. The loss of PHF5A results in an increased rate of apoptosis by triggering Fas- and unfolded protein response (UPR)-mediated apoptosis pathways in melanoma cells. These findings are tumour-specific because we did not observe this regulation in fibroblasts. Our study identifies a crucial role of PHF5A as driver for melanoma malignancy and the described underlying splicing network provides an interesting basis for the development of new therapeutic targets for this aggressive form of skin cancer.
2024 The Author(s). Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.
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