GPX8 regulates clear cell renal cell carcinoma tumorigenesis through promoting lipogenesis by NNMT

By analyzing RNAseq data from TCGA in ccRCC and metabolomics data from CCLE, we identified the strong correlation of GPX8 with the lipid and glycogen metabolism, which are highly upregulated in ccRCC. We validated this observation by knocking out GPX8 in Caki1 (ccRCC cell line). Using transcript profiling, we confirmed the association of GPX8 with de novo lipogenesis and suppressed fatty acid oxidation. Mechanically, from RNA-seq data we also found the decrease of NNMT upon GPX8 KO, which functions as the downstream of GPX8 and regulates the lipid phenotype in ccRCC. Overall design: GPX8 was permanently knocked out using CRISPR-Cas9 in Caki1 cell line. RNA samples from two groups (GPX8-KO Caki1 and WT-Caki1) were extracted for RNA sequencing.