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j.heliyon.2023.e18774.pdf | 4.44 MB | Adobe PDF | 見る/開く |
タイトル: | 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 |
著者: | Keng, Vincent W. Chiu, Amy P. To, Jeffrey C. Li, Xiao-Xiao Linden, Michael A. Amin, Khalid Moriarity, Branden S. Yusa, Kosuke |
著者名の別形: | 遊佐, 宏介 |
キーワード: | Hepatocellular carcinoma Transposable elements CRISPR Cas9 CTNNB1 NF2 |
発行日: | Aug-2023 |
出版者: | Elsevier BV |
誌名: | Heliyon |
巻: | 9 |
号: | 8 |
論文番号: | e18774 |
抄録: | Various molecular subclasses of hepatocellular carcinoma (HCC) exists, with many novel cooperating oncogenes and tumor suppressor genes involved in its tumorigenesis. The emerging importance of WNT signaling in HCC has been established. However, the intricate genetic mechanisms involved in this complex signaling pathway remains to be elucidated. Importantly, while some cooperating genes have been identified, there are still many unknown genes associated with catenin beta 1 (CTNNB1)-induced HCC. Mutations in both oncogenes and tumor suppressor genes are required for HCC tumorigenesis. The emergence of the CRISPR/Cas9 system has allowed researchers now to target both alleles efficiently. In this novel study, the Sleeping Beauty transposon system was used as a gene delivery system in vivo to stably integrate an expression cassette that carry pools of gRNAs and overexpress a mutant version of CTNNB1 into the hepatocyte genome. We identified 206 candidate genes that drive HCC tumorigenesis in the context of WNT signaling activation and, neurofibromin 2 (NF2) gene, a known tumor suppressor gene with clinical relevance was validated in this proof-of-principle study. |
著作権等: | © 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license. |
URI: | http://hdl.handle.net/2433/287028 |
DOI(出版社版): | 10.1016/j.heliyon.2023.e18774 |
PubMed ID: | 37576222 |
出現コレクション: | 学術雑誌掲載論文等 |
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