选择性剪接的异常是癌症形成的标志。在这项研究中，我们研究了剪接因子 PHD 指蛋白 5A (PHF5A) 在黑色素瘤中的作用。恶性黑色素瘤是最致命的皮肤癌，PHF5A 高表达的患者总体生存率较差。我们的数据显示，不同黑色素瘤细胞系中 siRNA 介导的 PHF5A 下调会导致不同肿瘤相关基因的大量剪接缺陷。 PHF5A 的缺失会触发黑色素瘤细胞中 Fas 和未折叠蛋白反应 (UPR) 介导的细胞凋亡途径，从而导致细胞凋亡率增加。这些发现是肿瘤特异性的，因为我们没有在成纤维细胞中观察到这种调节。我们的研究确定了 PHF5A 作为黑色素瘤恶性肿瘤驱动因素的关键作用，所描述的基础剪接网络为开发这种侵袭性皮肤癌的新治疗靶点提供了有趣的基础。© 2024 作者。北京干细胞与再生医学研究院和John Wiley联合出版的《细胞增殖》

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.