biostudies-literatureUnknown67(2)Zhang Y<h4>Purpose</h4>Mitochondrial dysfunction is increasingly recognized as a pivotal factor in cancer pathogenesis. We thus explored the causal role of mitochondrial-related genes (MRGs) in uveal melanoma (UM) and the underlying mechanisms.<h4>Methods</h4>We performed Mendelian randomization (MR) analysis using 1693 cis-expression quantitative trait loci (cis-eQTLs) of MRGs as instrumental variables and genome-wide association data (GWAS) of UM. Colocalization analysis assessed whether gene expression and UM risk shared a common causal variant. Further, mediation MR and in vitro functional assays were used to validate key findings and explore their biological relevance. A molecular docking-based virtual screening strategy, followed by experimental validation, was used to identify potential thInvestigative ophthalmology & visual science30https://www.ebi.ac.uk/biostudies/studies/S-EPMC12908717biostudies-literatureMTG2 as a Causal and Druggable Target in Uveal Melanoma via Mitochondrial DNA Dynamics: Evidence From Functional Validation and DMSA Identification.PMC12908717Shen ZZhang YMin DYu WWang YSu YFeng CCui BfalseMTG2 as a Causal and Druggable Target in Uveal Melanoma via Mitochondrial DNA Dynamics: Evidence From Functional Validation and DMSA Identification.<h4>Purpose</h4>Mitochondrial dysfunction is increasingly recognized as a pivotal factor in cancer pathogenesis. We thus explored the causal role of mitochondrial-related genes (MRGs) in uveal melanoma (UM) and the underlying mechanisms.<h4>Methods</h4>We performed Mendelian randomization (MR) analysis using 1693 cis-expression quantitative trait loci (cis-eQTLs) of MRGs as instrumental variables and genome-wide association data (GWAS) of UM. Colocalization analysis assessed whether gene expression and UM risk shared a common causal variant. Further, mediation MR and in vitro functional assays were used to validate key findings and explore their biological relevance. A molecular docking-based virtual screening strategy, followed by experimental validation, was used to identify potential th2026-01-01T00:00:00Z2026 Feb2026-07-15T22:19:17.658Z2026-07-09T10:20:36.595ZS-EPMC129087174167738810.1167/iovs.67.2.30