CHAF1B promotes the progression of lung squamous-cell carcinoma by inhibiting SETD7 expression.
10.1007/s11684-024-1122-2
- Author:
Zhuo ZHENG
1
;
Yongfang LIN
2
;
Hua GUO
2
;
Zheng LIU
2
;
Xiaoliang JIE
2
;
Guizhen WANG
2
;
Guangbiao ZHOU
3
Author Information
1. Guizhou University Medical College, Guiyang, 550025, China.
2. 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.
3. Guizhou University Medical College, Guiyang, 550025, China. gbzhou@cicams.ac.cn.
- Publication Type:Journal Article
- Keywords:
CHAF1B;
SETD7;
WGCNA;
cell cycle;
lung squamous cell carcinoma
- MeSH:
Humans;
Lung Neoplasms/metabolism*;
Histone-Lysine N-Methyltransferase/metabolism*;
Carcinoma, Squamous Cell/metabolism*;
Gene Expression Regulation, Neoplastic;
Disease Progression;
Cell Proliferation/genetics*;
Cell Line, Tumor;
Chromatin Assembly Factor-1/metabolism*;
Animals;
Mice;
Male;
Female
- From:
Frontiers of Medicine
2025;19(2):318-328
- CountryChina
- Language:English
-
Abstract:
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.
