ADARp110 promotes hepatocellular carcinoma progression via stabilization of CD24 mRNA

• DOI: 10.1073/pnas.2409724122
• Publication Date: 2025-01-14T18:37:30Z
• Authors: Liangzhan Sun; Pengchao Hu; Hui Yang; Jun Ren; Rong Hu; Shasha Wu; Yanchen Wang; Yuyang Du; Jingyi Zheng; Fenfen Wang; Han Gao; Jingsong Yan; Yun-Fei Yuan; Xin-Yuan Guan; Jia Xiao; Yan Li
• Keywords: CD24

ADAR is highly expressed and correlated with poor prognosis in hepatocellular carcinoma (HCC), yet the role of its constitutive isoform ADARp110 tumorigenesis remains elusive. We investigated HCC underlying mechanisms using clinical samples, a hepatocyte-specific Adarp110 knock-in mouse model, engineered cell lines. overexpressed associated survival both human HCC. It creates an immunosuppressive microenvironment by inhibiting total immune cells, particularly cytotoxic GZMB+CD8+ T cells infiltration, while augmenting Treg MDSCs, exhausted CD8+ ratios. Mechanistically, interacts SNRPD3 RNPS1 to stabilize CD24 mRNA STAU1-mediated decay. protects from two indispensable mechanisms: macrophage phagocytosis oxidative stress. Genetic knockdown or monoclonal antibody treatment inhibits ADARp110-overexpressing tumor growth. Our findings unveil different for modulation identify as promising therapeutic target HCCs.