PRBM1 inactivation promotes upregulation of human endogenous retroviruses in a HIF-dependent manner

By analyzing RNAseq data derived from TCGA and clinical trial in ccRCC we observed that PBRM1 mutation is significantly associated with expression changes of hERVs (human endogenous retroviruses). We validated this observation in UMRC2 cell line and further demonstrated that PBRM1 specifically regulated members of HERVERI superfamily. We found that the increased expression of hERVs by loss of PBRM1 reversed by further knocking down HIF complex. Our data indicated a role of PBRM1 in negative regulation of selective hERVs in a HIF-dependent manner Overall design: PBRM1 was permanently knocking down by shRNA in UMRC2 cell line. siRNA of HIF1a and HIF2a was used to further knock down HIF1a and HIF1b in the PBRM1 kd cells. With two biological replicates for each condition, there are 24 samples in total to be collected for RNA extraction and subsequently RNA sequencing.