ZNF296 drives immune evasion in epithelial cancer cells [RNA-seq]

Using a genome-wide CRISPR activation screen, we identified ZNF296, a transcription factor prominently expressed in epithelial cancers, as a key regulator of tumor resistance to NK cell-mediated cytotoxicity. To systematically investigate the mechanisms by which ZNF296 suppresses NK cell-mediated killing, RNA-seq analysis was performed on A549 cells overexpressing ZNF296 (ZNF296-OE), and 4T1 cells with knockdown of its murine homolog Zfp296 (Zfp296KD). By analyzing differential gene expression and signaling pathways, we aimed to understand the influence of ZNF296/Zfp296 on tumor-intrinsic mechanisms. To identify ZNF296-dependent transcriptional changes, bulk RNA-seq was conducted on cells with both ectopic and inhibited ZNF296 expression. ZNF296-overexpressing A549 cells were generated using a lentiviral expression system, while Zfp296 inhibition was achieved in 4T1 cells via the CRISPRi system.