biostudies-literatureNguyen TTMNational Research Foundation (KR)National Research Foundation42https://www.ebi.ac.uk/biostudies/studies/S-EPMC9903620biostudies-literatureUnknown42(1)<h4>Background</h4>Clear cell renal cell carcinoma (ccRCC), with its hallmark phenotype of high cytosolic lipid content, is considered a metabolic cancer. Despite the implication of this lipid-rich phenotype in ccRCC tumorigenesis, the roles and regulators of de novo lipid synthesis (DNL) in ccRCC remain largely unexplained.<h4>Methods</h4>Our bioinformatic screening focused on ccRCC-lipid phenotypes identified glutathione peroxidase 8 (GPX8), as a clinically relevant upstream regulator of DNL. GPX8 genetic silencing was performed with CRISPR-Cas9 or shRNA in ccRCC cell lines to dissect its roles. Untargeted metabolomics, RNA-seq analyses, and other biochemical assays (e.g., lipid droplets staining, fatty acid uptake, cell proliferation, xenograft, etc.) were carried out to investigate theJournal of experimental & clinical cancer research : CRGPX8 regulates clear cell renal cell carcinoma tumorigenesis through promoting lipogenesis by NNMT.PMC9903620NRF-2020R1I1A1A01073124NRF-2018R1A3B1052328Mai VHKim JMAn YJNguyen THKang SKim HSJung CRDao TTPSeo MPark SNguyen TTMMoon YfalseGPX8 regulates clear cell renal cell carcinoma tumorigenesis through promoting lipogenesis by NNMT.<h4>Background</h4>Clear cell renal cell carcinoma (ccRCC), with its hallmark phenotype of high cytosolic lipid content, is considered a metabolic cancer. Despite the implication of this lipid-rich phenotype in ccRCC tumorigenesis, the roles and regulators of de novo lipid synthesis (DNL) in ccRCC remain largely unexplained.<h4>Methods</h4>Our bioinformatic screening focused on ccRCC-lipid phenotypes identified glutathione peroxidase 8 (GPX8), as a clinically relevant upstream regulator of DNL. GPX8 genetic silencing was performed with CRISPR-Cas9 or shRNA in ccRCC cell lines to dissect its roles. Untargeted metabolomics, RNA-seq analyses, and other biochemical assays (e.g., lipid droplets staining, fatty acid uptake, cell proliferation, xenograft, etc.) were carried out to investigate the2023-01-01T00:00:00Z2023 Feb2025-05-29T19:43:41.846Z2025-04-04T12:55:55.586ZS-EPMC99036203675085010.1186/s13046-023-02607-2