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. 2025 Apr;19(2):318-328.
doi: 10.1007/s11684-024-1122-2. Epub 2025 Jan 25.

CHAF1B promotes the progression of lung squamous-cell carcinoma by inhibiting SETD7 expression

Zhuo Zheng  1   2 , Yongfang Lin  2 , Hua Guo  2 , Zheng Liu  2 , Xiaoliang Jie  2 , Guizhen Wang  2 , Guangbiao Zhou  3   4
Affiliations

CHAF1B promotes the progression of lung squamous-cell carcinoma by inhibiting SETD7 expression

Zhuo Zheng et al. Front Med. 2025 Apr.

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.

Keywords: CHAF1B; SETD7; WGCNA; cell cycle; lung squamous cell carcinoma.

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Conflict of interest statement

Compliance with ethics guidelines. Conflicts of interest Zhuo Zheng, Yongfang Lin, Hua Guo, Zheng Liu, Xiaoliang Jie, Guizhen Wang, and Guangbiao Zhou declare that they have no conflict of interest. The study was approved by the research ethics committee of the Cancer Hospital, Chinese Academy of Medical Sciences and performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Additional informed consent was obtained from all patients, whose identifying information is included in this article.

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