Li Junfeng, Fu Yuxia, Zhang Hongchuan, Ma Hong
Department of Oncology, Dianjiang People's Hospital of Chongqing, Chongqing, China.
Department of Ultrasound, Dianjiang People's Hospital of Chongqing, Chongqing, China.
Pathol Res Pract. 2025 Feb;266:155763. doi: 10.1016/j.prp.2024.155763. Epub 2024 Dec 9.
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide, with complex etiological factors and a diverse genetic landscape. Among the critical genetic mutations in HCC, the AT-rich interaction domain 1 A (ARID1A) gene, a key component of the SWI/SNF chromatin remodeling complex, stands out due to its significant role in both tumor suppression and oncogenesis. This review comprehensively examines the molecular and pathological impacts of ARID1A mutations in HCC. ARID1A mutations, which occur in approximately 7.9 % of HCC cases, predominantly involve truncating mutations leading to loss of function. These mutations are associated with various aggressive cancer features, including larger tumor size, higher rates of metastasis, and poor prognosis. The dual role of ARID1A in HCC is context-dependent, acting as a tumor suppressor by regulating cell cycle control, DNA damage repair, and gene expression, while also displaying oncogenic properties in specific contexts by promoting early tumorigenesis through oxidative stress pathways. Understanding the molecular mechanisms of ARID1A, including its interactions with key cellular pathways such as PI3K/AKT/mTOR, β-catenin, and PD-L1, provides insights into its complex role in HCC pathogenesis. Furthermore, ARID1A's impact on cancer stem cell maintenance, metabolic reprogramming, and immune evasion underscores its potential as a therapeutic target. This review highlights the need for context-specific therapeutic strategies targeting ARID1A, which could lead to more effective treatments for HCC, addressing both its tumor-suppressive and oncogenic activities.
肝细胞癌（HCC）是全球癌症相关死亡的主要原因之一，其病因复杂，基因图谱多样。在HCC的关键基因突变中，富含AT的相互作用结构域1A（ARID1A）基因作为SWI/SNF染色质重塑复合体的关键组成部分脱颖而出，因其在肿瘤抑制和肿瘤发生中均发挥着重要作用。本综述全面探讨了ARID1A突变在HCC中的分子和病理影响。ARID1A突变约发生在7.9%的HCC病例中，主要涉及导致功能丧失的截短突变。这些突变与各种侵袭性癌症特征相关，包括更大的肿瘤尺寸、更高的转移率和不良预后。ARID1A在HCC中的双重作用取决于具体情况，通过调节细胞周期控制、DNA损伤修复和基因表达发挥肿瘤抑制作用，同时在特定情况下也通过氧化应激途径促进早期肿瘤发生而表现出致癌特性。了解ARID1A的分子机制，包括其与PI3K/AKT/mTOR、β-连环蛋白和PD-L1等关键细胞途径的相互作用，有助于深入了解其在HCC发病机制中的复杂作用。此外，ARID1A对癌症干细胞维持、代谢重编程和免疫逃逸的影响突出了其作为治疗靶点的潜力。本综述强调了针对ARID1A的特定背景治疗策略的必要性，这可能会为HCC带来更有效的治疗方法，同时应对其肿瘤抑制和致癌活性。
