ARID1A, an SWI/SNF chromatin-remodeling gene, is commonly mutated in cancer and hypothesized to be tumor suppressive. In some hepatocellular carcinoma patients, ARID1A was highly expressed in primary tumors but not in metastatic lesions, suggesting that ARID1A can be lost after initiation. Mice with liver-specific homozygous or heterozygous Arid1a loss were resistant to tumor initiation while ARID1A overexpression accelerated initiation. In contrast, homozygous or heterozygous Arid1a loss in established tumors accelerated progression and metastasis. Mechanistically, gain of Arid1a function promoted initiation by increasing CYP450-mediated oxidative stress, while loss of Arid1a within tumors decreased chromatin accessibility and reduced transcription of genes associated with migration, invasion, and metastasis. In summary, ARID1A has context-dependent tumor-suppressive and oncogenic roles in cancer.

中文翻译：

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Arid1a在肝癌中具有上下文相关的致癌和肿瘤抑制功能。

ARID1A是SWI / SNF染色质重塑基因，通常在癌症中发生突变，并被认为具有抑癌作用。在一些肝细胞癌患者中，ARID1A在原发性肿瘤中高表达，但在转移性病变中不高，提示ARID1A可能在开始后消失。具有肝脏特异性纯合子或杂合子Arid1a缺失的小鼠对肿瘤的起始有抵抗力，而ARID1A过表达则加速了起始。相反，在已建立的肿瘤中纯合或杂合的Arid1a丢失加速了进展和转移。从机制上讲，Arid1a功能的获得通过增加CYP450介导的氧化应激而促进了启动，而肿瘤中Arid1a的丧失降低了染色质的可及性并减少了与迁移，侵袭和转移相关的基因转录。总之，