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APOBEC3B/ASF1B-TGF-β signaling axis promotes epithelial-mesenchymal transition in HPV-positive oropharyngeal cancer
Ming-Shou Hsieh1,2, Chih-Chi Sheen1,2, Tung-Nien Hsu1,2
1School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan.
Background/Purpose:
Human papillomavirus (HPV)-positive oropharyngeal cancer (OPC) generally shows better outcomes, yet a subset of patients develops aggressive lymphatic metastasis. The molecular determinants of this divergence remain unclear. This study explored the apolipoprotein B mRNA editing enzyme catalytic subunit 3B (APOBEC3B)/anti-silencing function 1B histone chaperone (ASF1B) axis as a potential mediator linking human papillomavirus (HPV) infection, DNA damage, and transforming growth factor beta (TGF-β) signaling in OPC.
Materials And Methods:
Transcriptomic and clinical datasets from The Cancer Genome Atlas (TCGA) were analyzed to examine correlations among APOBEC3B/ASF1B expression, HPV status, and TGF-β signaling activity. Functional assays using HPV-positive and HPV-negative cell models assessed APOBEC3B/ASF1B expression, replication protein A2 (RPA2) activation, and epithelial-mesenchymal transition (EMT) markers through quantitative polymerase chain reaction (qPCR), western blotting, and immunofluorescence.
Results:
HPV infection markedly enhanced APOBEC3B and ASF1B expression, accompanied by RPA2 upregulation and EMT features. Silencing APOBEC3B reduced RPA2 and ASF1B levels and suppressed TGF-β signaling.
Conclusion:
These findings identify APOBEC3B/ASF1B as a central pathway through which HPV infection activates TGF-β signaling and promotes EMT, offering potential biomarkers and therapeutic targets for high-risk HPV-positive OPC.
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