Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Cell Prolif. 2020 Apr;53(4):e12791. doi: 10.1111/cpr.12791. Epub 2020 Mar 11.
Hepatocellular carcinoma (HCC) is a primary liver malignancy with a high global prevalence and a dismal prognosis. Studies are urgently needed to examine the molecular pathogenesis and biological characteristics of HCC. Chromatin remodelling, an integral component of the DNA damage response, protects against DNA damage-induced genome instability and tumorigenesis by triggering the signalling events that activate the interconnected DNA repair pathways. The SWI/SNF complexes are one of the most extensively investigated adenosine triphosphate-dependent chromatin remodelling complexes, and mutations in genes encoding SWI/SNF subunits are frequently observed in various human cancers, including HCC. The mutated SWI/SNF complex subunits exert dual functions by accelerating or inhibiting HCC initiation and progression. Furthermore, the abnormal SWI/SNF complexes influence the transcription of interferon-stimulated genes, as well as the differentiation, activation and recruitment of several immune cell types. In addition, they exhibit synergistic effects with immune checkpoint inhibitors in the treatment of diverse tumour types. Therefore, understanding the mutations and deficiencies of the SMI/SNF complexes, together with the associated functional mechanisms, may provide a novel strategy to treat HCC through targeting the related genes or modulating the tumour microenvironment.
肝细胞癌（HCC）是一种原发性肝脏恶性肿瘤，具有较高的全球发病率和较差的预后。目前迫切需要研究 HCC 的分子发病机制和生物学特征。染色质重塑是 DNA 损伤反应的一个组成部分，通过触发激活相互关联的 DNA 修复途径的信号事件，保护细胞免受 DNA 损伤诱导的基因组不稳定性和肿瘤发生。SWI/SNF 复合物是研究最广泛的腺苷三磷酸依赖性染色质重塑复合物之一，编码 SWI/SNF 亚基的基因突变在包括 HCC 在内的多种人类癌症中经常观察到。突变的 SWI/SNF 复合物亚基通过加速或抑制 HCC 的起始和进展发挥双重功能。此外，异常的 SWI/SNF 复合物会影响干扰素刺激基因的转录，以及多种免疫细胞类型的分化、激活和募集。此外，它们在治疗多种肿瘤类型的免疫检查点抑制剂中具有协同作用。因此，了解 SMI/SNF 复合物的突变和缺陷，以及相关的功能机制，可能为通过靶向相关基因或调节肿瘤微环境来治疗 HCC 提供一种新策略。
