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• W4297520321 abstract "Abstract Aberrant adenosine-to-inosine (A-to-I) RNA editing, catalyzed by adenosine deaminase acting on double-stranded RNA (ADAR), is implicated in various cancers, but the mechanisms by which microRNA (miRNA) editing contributes to cancer development are currently largely unknown. Our multi-step hepatocellular carcinogenesis transcriptome data analyses, together with publicly available data, indicated that ADAR1 is the most dysregulated gene among the RNA editing enzyme families in liver cancer. Targeted inactivation of ADAR1 inhibits in vitro tumorigenesis of liver cancer cells. Integrative computational analyses of RNA editing hotspots and the editing frequency of miRNAs suggested miR-3144-3p a potential mRNA edited by ADAR1 in liver cancer progression. ADAR1 promoted A-to-I editing of the canonical miR-3144-3p to change position 3 adenosine in the seed region to guanine (ED_miR-3144-3p(3_A < G)) in liver cancer cells. We then demonstrated that Musashi RNA-binding protein 2 ( MSI2 ) is a specific target of miR-3144-3p, and that MSI2 overexpression is due to ADAR1-dependent over-editing of the canonical miR-3144-3p in liver cancer. In addition, target prediction analyses and validation experiments identified solute carrier family 38 member 4 ( SLC38A4 ) as specific target gene for ED_miR-3144-3p(3_A < G). Ectopic expressions of both ADAR1 and ED_miR-3144-3p(3_A < G) mimics enhanced mitotic activities and that ADAR1 suppressed SLC38A4 in liver cancer cells. Treatments with mouse-specific ADAR1-, MSI2-siRNA or SLC39A4-expressing plasmids suppressed tumor incidence and growth in a spontaneous mouse liver cancer model. Our findings suggest that aberrant regulation of ADAR1 augments oncogenic MSI2 via overediting the canonical miR-3144-3p, and the resultant ED_miR-3144-3p(3_A < G) simultaneously suppresses tumor suppressor SLC38A4, thereby contributing to hepatocellular carcinogenesis." @default.
• W4297520321 created "2022-09-29" @default.
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• W4297520321 date "2022-09-28" @default.
• W4297520321 modified "2023-09-27" @default.
• W4297520321 title "ADAR1-dependent miR-3144-3p editing simultaneously induces MSI2 and suppresses SLC38A4 in liver cancer" @default.
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• W4297520321 doi "https://doi.org/10.21203/rs.3.rs-1999877/v1" @default.
• W4297520321 hasPublicationYear "2022" @default.
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