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Transcriptomic sequencing highlights PURPL as one of the top upregulated long noncoding RNAs in response to ionizing radiation (IR) treatment in melanoma cells, suggesting its role in radioresistance. To explore such hypothesis, loss\u2010of\u2010function experiments were conducted to assess the impact of PURPL on melanoma cell viability, colony formation, and migration. Mechanistic studies using RNA pulldown identified BID as the interacting protein partner of PURPL. Further analysis explored the relationship among PURPL, BID, and Caspase\u20108 in the context of IR\u2010induced DNA damage and apoptosis through loss\u2010of\u2010 and gain\u2010of\u2010function experiments. The findings demonstrated that silencing PURPL significantly repressed melanoma cell viability, colony formation, migration, and invasiveness, indicating its potential role in promoting radioresistance. Moreover, PURPL was shown to repress IR\u2010induced DNA damage and apoptosis, supporting its involvement in melanoma radioresistance. Mechanistically, PURPL inhibited the interaction between BID and Caspase\u20108, thereby modulating the mitochondrial apoptosis pathway and promoting radioresistance. In conclusion, this study provides evidence supporting the pro\u2010radioresistance role of PURPL in melanoma. In\u00a0vivo assays further corroborated the in\u00a0vitro findings, highlighting the potential clinical relevance of targeting PURPL in radioresistant melanoma. By interfering with the association between BID and Caspase\u20108, PURPL may serve as a novel therapeutic target for clinical radiotherapy during the treatment of melanoma.<\/jats:p>","DOI":"10.1111\/pcmr.70018","type":"journal-article","created":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T04:07:22Z","timestamp":1744690042000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["<scp>PURPL<\/scp> Represses Radiation\u2010Induced Apoptosis to Promote Radioresistance in Cutaneous Melanoma by Direct Interfering With <scp>BID<\/scp> Cleavage"],"prefix":"10.1111","volume":"38","author":[{"given":"Xue","family":"Li","sequence":"first","affiliation":[{"name":"Institute of Molecular Immunology School of Laboratory Medicine and Biotechnology, Southern Medical University  Guangzhou China"},{"name":"Department of Clinical Medical Technology Sichuan Vocational College of Health and Rehabilitation  Zigong 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