Smoking-associated upregulation of CBX3 suppresses ARHGAP24 expression to activate Rac1 signaling and promote tumor progression in lung adenocarcinoma

Although tobacco smoking is a risk factor for lung adenocarcinoma (LUAD), the mechanisms by which tobacco smoking induces LUAD development remain elusive. Histone methylation levels in human bronchial epithelial cells have been reported to increase after exposure to cigarettes. In this study, we exp...

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Bibliographic Details
Published in:Oncogene 2022-01, Vol.41 (4), p.538-549
Main Authors: Jin, Xin, Zhang, Bin, Zhang, Hao, Yu, Haixin
Format: Article
Language:English
Subjects:
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Adenocarcinoma
Adenocarcinoma of Lung - etiology
Adenocarcinoma of Lung - pathology
Animals
Apoptosis
Cancer
Cell Biology
Cell Line, Tumor
Chromosomal Proteins, Non-Histone - metabolism
Cigarettes
Epithelial cells
GTPase-Activating Proteins - metabolism
Histones
Human Genetics
Humans
Internal Medicine
Lung cancer
Lung Neoplasms - etiology
Lung Neoplasms - pathology
Medicine
Medicine & Public Health
Methylation
Mice
Mice, Nude
Oncology
rac1 GTP-Binding Protein - metabolism
Rac1 protein
Risk factors
Smoking
Therapeutic targets
Tobacco smoking
Tobacco Smoking - adverse effects
Tumors
Up-Regulation
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Summary:Although tobacco smoking is a risk factor for lung adenocarcinoma (LUAD), the mechanisms by which tobacco smoking induces LUAD development remain elusive. Histone methylation levels in human bronchial epithelial cells have been reported to increase after exposure to cigarettes. In this study, we explored the mechanisms regulating histone methylation in LUAD in response to smoking. We found that the histone H3K9 methylation reader CBX3 was upregulated in current smokers with LUAD, and that CBX3 overexpression promoted LUAD progression. Functional enrichment analyses revealed that CBX3 regulated the activation of Rho GTPases in LUAD. We also found that by forming a complex with TRIM28, TRIM24, and RBBP4, CBX3 repressed the expression of ARHGAP24 and increased the amount of active Rac1 in LUAD cells. Collectively, these results suggest that smoking associated upregulation of CBX3 promotes LUAD progression by activating the ARHGAP24/Rac1 pathway. Hence, the CBX3/ARHGAP24/Rac1 axis may represent a promising therapeutic target in smoking-induced LUAD.
ISSN:0950-9232
1476-5594
DOI:10.1038/s41388-021-02114-8