Zheng Zhuo, Lin Yongfang, Guo Hua, Liu Zheng, Jie Xiaoliang, Wang Guizhen, Zhou Guangbiao
Guizhou University Medical College, Guiyang, 550025, China.
State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
Front Med. 2025 Apr;19(2):318-328. doi: 10.1007/s11684-024-1122-2. Epub 2025 Jan 25.
The p60 subunit of the chromatin assembly factor-1 complex, that is, chromatin assembly factor-1 subunit B (CHAF1B), is a histone H3/H4 chaperone crucial for the transcriptional regulation of cell differentiation and self-renewal. CHAF1B is overexpressed in several cancers and may represent a potential target for cancer therapy. However, its expression and clinical significance in lung squamous-cell carcinoma (LUSC) remain unclear. In this study, we performed weighted gene correlation network analysis to analyze the Gene Expression Omnibus GSE68793 LUSC dataset and identified CHAF1B as one of the most important driver gene candidates. Immunohistochemical analysis of 126 LUSC tumor samples and 80 adjacent normal lung tissues showed the marked upregulation of CHAF1B in tumor tissues and the negative association of its expression level with patient survival outcomes. Silencing of CHAF1B suppressed LUSC proliferation in vitro and LUSC tumor growth in vivo. Furthermore, bulk RNA sequencing of CHAF1B knockdown cells indicated SET domain containing 7 (SETD7) as a significant CHAF1B target gene. In addition, CHAF1B competitively binds to the SETD7 promoter region and represses its transcription. Altogether, these results imply that CHAF1B plays a vital role in LUSC tumorigenesis and may represent a potential molecular target for this deadly disease.
染色质组装因子-1复合物的p60亚基，即染色质组装因子-1亚基B（CHAF1B），是一种组蛋白H3/H4分子伴侣，对细胞分化和自我更新的转录调控至关重要。CHAF1B在几种癌症中过表达，可能是癌症治疗的潜在靶点。然而，其在肺鳞状细胞癌（LUSC）中的表达及临床意义仍不清楚。在本研究中，我们进行了加权基因共表达网络分析，以分析基因表达综合数据库GSE68793中的LUSC数据集，并确定CHAF1B是最重要的驱动基因候选者之一。对126例LUSC肿瘤样本和80例相邻正常肺组织进行免疫组织化学分析，结果显示肿瘤组织中CHAF1B明显上调，其表达水平与患者生存结果呈负相关。CHAF1B沉默抑制了LUSC的体外增殖和体内肿瘤生长。此外，对CHAF1B敲低细胞进行的大量RNA测序表明，含SET结构域7（SETD7）是CHAF1B的一个重要靶基因。此外，CHAF1B竞争性结合SETD7启动子区域并抑制其转录。总之，这些结果表明CHAF1B在LUSC肿瘤发生中起重要作用，可能是这种致命疾病的潜在分子靶点。
