2026-10-14T06:24:32Z https://www.scidb.cn/oai

10.57760/sciencedb.45658 2026-08-07T10:19:55Z

2026-08-07 Integrated Multi-Omics Analysis Uncovers SELENOP and TAF10 as Mechanistically Distinct Therapeutic Targets in ccRCC through Lactate Metabolism and EMT Regulation with Repurposing of Diosmin and Micafungin Sodium doi:10.57760/sciencedb.45658 en Background: Clear cell renal cell carcinoma (ccRCC) features metabolic reprogramming and epithelial–mesenchymal transition crosstalk that remains poorly understood. Methods: We integrated scRNA-seq from three cohorts with TCGA/GEO bulk transcriptomic data, constructed a 15-gene LASSO prognostic risk model using differentially expressed genes, performed CRISPR-Cas9 functional studies in A498 and OS-RC-2 cells and xenograft models, and conducted structure-based virtual screening with molecular dynamics simulations to identify repurposable drugs targeting SELENOP and TAF10. Results: The 15-gene signature stratified patients by survival and immune landscape across multiple validation cohorts. SELENOP suppressed BSG-mediated lactate export, whereas TAF10 drove SRGN-dependent EMT. Virtual screening identified Diosmin and Micafungin Sodium as SELENOP agonist and TAF10 antagonist, both showing anti-tumor efficacy preclinically with synergistic combination effects. Conclusions: SELENOP and TAF10 represent mechanistically distinct therapeutic targets via BSG–lactate and SRGN–EMT pathways, and Diosmin with Micafungin Sodium merit clinical investigation as ccRCC repurposed therapeutics. Clear cell renal cell carcinoma; Amino acid metabolism; SELENOP; TAF10; Epithelial–mesenchymal transition; Drug repurposing; Prognostic model Jiangbei Yuan PUBLIC https://creativecommons.org/licenses/by-nc-sa/4.0/ dataset Science Data Bank