CRISPR activation screening in a mouse model for drivers of hepatocellular carcinoma growth and metastasis

Hepatocellular carcinoma (HCC) remains a major cause of cancer-related mortality worldwide. Here we described a genome-wide screen by CRISPR activation (CRISPRa) library in vivo for drivers of HCC growth and metastasis. Pathological results showed the cell population formed highly metastatic tumors in lung after being mutagenized with CRISPRa. In vitro validation indicated overexpression of XAGE1B, PLK4, LMO1 and MYADML2 promoted cells proliferation and invasion, and the inhibition suppressed HCC progress. In addition, we reported high MYADML2 protein level exhibited worse overall survival in HCC, which increased significantly in patients over 60 years. Moreover, high MYADML2 reduced the sensitivity to chemotherapeutic drugs. Interestingly, immune cell infiltration analysis showed that the dendritic cells, macrophages, and so forth might play important role in HCC progress. In brief, we provides a roadmap for screening functional genes related to HCC invasion and metastasis in vivo, which may provide new potential targets for the treatment of HCC. [Display omitted] •We develop CRISPRa screen for driver of HCC invasion and metastasis in vivo•The screen uncovered 4 novel modulator targets:XAGE1B, PLK4, LMO1 and MYADML2•High MYADML2 exhibited worse overall survival in HCC and reduced drug sensitivity Molecular biology; Cell biology; Cancer