{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T03:57:38Z","timestamp":1785815858116,"version":"3.56.0"},"reference-count":133,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T00:00:00Z","timestamp":1720656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"DAAD Ta\u2019ziz project","award":["57682181"],"award-info":[{"award-number":["57682181"]}]},{"name":"DAAD Ta\u2019ziz project","award":["57522433"],"award-info":[{"award-number":["57522433"]}]},{"name":"German Academic Exchange Service (DAAD)","award":["57682181"],"award-info":[{"award-number":["57682181"]}]},{"name":"German Academic Exchange Service (DAAD)","award":["57522433"],"award-info":[{"award-number":["57522433"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>A transcriptome-wide association study (TWAS) was conducted on genome-wide association study (GWAS) summary statistics of malignant melanoma of skin (UK Biobank dataset) and The Cancer Genome Atlas-Skin Cutaneous Melanoma (TCGA-SKCM) gene expression weights to identify melanoma susceptibility genes. The GWAS included 2465 cases and 449,799 controls, while the gene expression testing was conducted on 103 cases. Afterward, a gene enrichment analysis was applied to identify significant TWAS associations. The melanoma\u2019s gene\u2013microRNA (miRNA) regulatory network was constructed from the TWAS genes and their corresponding miRNAs. At last, a disease enrichment analysis was conducted on the corresponding miRNAs. The TWAS detected 27 genes associated with melanoma with p-values less than 0.05 (the top three genes are LOC389458 (RBAK), C16orf73 (MEIOB), and EIF3CL). After the joint\/conditional test, one gene (AMIGO1) was dropped, resulting in 26 significant genes. The Gene Ontology (GO) biological process associated the extended gene set (76 genes) with protein K11-linked ubiquitination and regulation of cell cycle phase transition. K11-linked ubiquitin chains regulate cell division. Interestingly, the extended gene set was related to different skin cancer subtypes. Moreover, the enriched pathways were nsp1 from SARS-CoV-2 that inhibit translation initiation in the host cell, cell cycle, translation factors, and DNA repair pathways full network. The gene-miRNA regulatory network identified 10 hotspot genes with the top three: TP53, BRCA1, and MDM2; and four hotspot miRNAs: mir-16, mir-15a, mir-125b, and mir-146a. Melanoma was among the top ten diseases associated with the corresponding (106) miRNAs. Our results shed light on melanoma pathogenesis and biologically significant molecular interactions.<\/jats:p>","DOI":"10.3390\/cancers16142517","type":"journal-article","created":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T11:33:22Z","timestamp":1720697602000},"page":"2517","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Transcriptome-Wide Association Study Reveals New Molecular Interactions Associated with Melanoma Pathogenesis"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8229-0280","authenticated-orcid":false,"given":"Mohamed N.","family":"Saad","sequence":"first","affiliation":[{"name":"Biomedical Engineering Department, Faculty of Engineering, Minia University, Minia 61519, Egypt"},{"name":"Institute for Biostatistics and Informatics in Medicine and Ageing Research (IBIMA), Rostock University Medical Center, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9102-8839","authenticated-orcid":false,"given":"Mohamed","family":"Hamed","sequence":"additional","affiliation":[{"name":"Institute for Biostatistics and Informatics in Medicine and Ageing Research (IBIMA), Rostock University Medical Center, 18057 Rostock, Germany"},{"name":"Faculty of Media Engineering and Technology, German University in Cairo, Cairo 11835, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Bush, W.S., and Moore, J.H. 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