ADARp110 promotes hepatocellular carcinoma progression via stabilization of CD24 mRNA

被引：0

作者：

Sun, Liangzhan ^{[1
,2
,3
,4
,5
]}

Hu, Pengchao ^{[1
,6
]}

Yang, Hui ^{[1
]}

Ren, Jun ^{[1
]}

Hu, Rong ^{[1
]}

Wu, Shasha ^{[1
]}

Wang, Yanchen ^{[7
]}

Du, Yuyang ^{[1
]}

Zheng, Jingyi ^{[7
]}

Wang, Fenfen ^{[1
]}

Gao, Han ^{[1
]}

Yan, Jingsong ^{[1
]}

Yuan, Yun-Fei ^{[8
]}

Guan, Xin-Yuan ^{[2
,3
]}

Xiao, Jia ^{[9
]}

Li, Yan ^{[7
]}

机构：

[1] Southern Univ Sci & Technol, Sch Life Sci, Dept Syst Biol, Shenzhen 518055, Peoples R China

[2] Univ Hong Kong, Dept Clin Oncol, Hong Kong 999077, Peoples R China

[3] Univ Hong Kong, State Key Lab Liver Res, Hong Kong 999077, Peoples R China

[4] Inst Canc Res, Shenzhen Bay Lab, Shenzhen 518067, Peoples R China

[5] Peking Univ, Shenzhen Grad Sch, Shenzhen 518055, Peoples R China

[6] Hubei Univ Med, Xiangyang Peoples Hosp 1, Dept Oncol, Xiangyang 441000, Peoples R China

[7] Southern Med Univ, Shenzhen Hosp, Shenzhen 518000, Peoples R China

[8] Sun Yat Sen Univ, Canc Ctr, State Key Lab Oncol Southern China, Guangzhou 510060, Peoples R China

[9] Jinan Univ, Guangdong Prov Key Lab Tumor Intervent Diag & Trea, Zhuhai Hosp, Zhuhai 519000, Peoples R China

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2025年 / 122卷 / 03期

关键词：

ADARp110; hepatocellular carcinoma; macrophage; phagocytosis; CD24; EXPRESSION; CELLS;

D O I：

10.1073/pnas.2409724122

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

ADAR is highly expressed and correlated with poor prognosis in hepatocellular carcinoma (HCC), yet the role of its constitutive isoform ADARp110 in tumorigenesis remains elusive. We investigated the role of ADARp110 in HCC and underlying mechanisms using clinical samples, a hepatocyte- specificAdarp110 knock- in mouse model, and engineered cell lines. ADARp110 is overexpressed and associated with poor survival in both human and mouse HCC. It creates an immunosuppressive microenvironment by inhibiting total immune cells, particularly cytotoxic GZMB+CD8+ T cells infiltration, while augmenting Treg cells, MDSCs, and exhausted CD8+T cells ratios. Mechanistically, ADARp110 interacts with SNRPD3 and RNPS1 to stabilize CD24 mRNA by inhibiting STAU1- mediated mRNA decay. CD24 protects HCC cells from two indispensable mechanisms: macrophage phagocytosis and oxidative stress. Genetic knockdown or monoclonal antibody treatment of CD24 inhibits ADARp110- overexpressing tumor growth. Our findings unveil different mechanisms for ADARp110 modulation of tumor immune microenvironment and identify CD24 as a promising therapeutic target for HCCs.

引用

页数：12

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