Transposon delivery for CRISPR-based loss-of-function screen in mice identifies NF2 as a cooperating gene involved with the canonical WNT signaling molecular class of hepatocellular carcinoma

• DOI: 10.1016/j.heliyon.2023.e18774
• Publication Date: 2023-07-28T01:45:02Z
• Authors: Vincent W. Keng; Amy P. Chiu; Jeffrey C. To; Xiao-Xiao Li; Michael A. Linden; Khalid Amin; Branden S. Moriarity; Kosuke Yusa
• Keywords: Social sciences (General); H1-99; Q1-390; Science (General); Hepatocellular carcinoma; CRISPR; NF2; CTNNB1; Cas9; Transposable elements; CRISPR/Cas9; Research Article

Various molecular subclasses of hepatocellular carcinoma (HCC) exists, with many novel cooperating oncogenes and tumor suppressor genes involved in its tumorigenesis. The emerging importance WNT signaling HCC has been established. However, the intricate genetic mechanisms this complex pathway remains to be elucidated. Importantly, while some have identified, there are still unknown associated catenin beta 1 (CTNNB1)-induced HCC. Mutations both required for emergence CRISPR/Cas9 system allowed researchers now target alleles efficiently. In study, Sleeping Beauty transposon was used as a gene delivery vivo stably integrate an expression cassette that carry pools gRNAs overexpress mutant version CTNNB1 into hepatocyte genome. We identified 206 candidate drive tumorigenesis context activation and, neurofibromin 2 (NF2) gene, known clinical relevance validated proof-of-principle study.