CRISPR/Cas9 genome-wide screen and transcriptome profiling in a MYC-conditional HCC model [CRISPR]

The MYC oncogene is often dysregulated in human cancer, including hepatocellular carcinoma (HCC). However, MYC is considered undruggable to date. Here, we comprehensively identify genes essential for the survival of MYC-high but not MYC-low cells by performing a CRISPR/Cas9 genome-wide screen in a MYC-conditional HCC model. Our screen identifies novel MYC-synthetic lethal interactions, as well as most previously identified MYC-synthetic lethal genes. In particular, we found genes involved in nuclear to cytoplasmic transport to be MYC-synthetic lethal in HCC, and we show that many of these genes are transcriptionally upregulated in MYC-high murine HCC. Pooled CRISPR library screen was performed on conditional MYC-HCC-derived mouse cells (EC4 cells) with MYC high and MYC low.