Ubiquitin-like with phd and ring finger domains 1 as a potential therapeutic target in smoking-associated oral squamous cell carcinoma

Authors

Yi-Shing Shieh, Department of Dentistry, Tri-Service General Hospital, National Defense Medical Center
Jia-Rong Wu, Graduate Institute of Life Sciences, National Defense Medical Center
Che-Ting Yeh, School of Dentistry, National Defense Medical Center
Chu-Yen Chien, Graduate Institute of Medical Sciences, National Defense Medical Center
Ying-Chen Chen, Molecular and Cell Biology, Taiwan International Graduate Program, Academia Sinica and Graduate Institute of Life Science, National Defense Medical Center
Tsai-Wang Huang, Division of Thoracic Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center
Che-Yi Lin, Department of Oral and Maxillofacial Surgery, Chi Mei Medical Center
Alexander Cheng-Ting Hsieh, Department of Medical Education, Tri-Service General Hospital, National Defense Medical Center
Yi-Jen Hung, Tri-Service General Hospital Division of Endocrinology and Metabolism, National Defense Medical Center

DOI

10.1016/j.jds.2025.04.011

First Page

1772

Last Page

1781

Abstract

Abstract Background/purpose Oral squamous cell carcinoma (OSCC) is a prevalent and aggressive malignancy with poor clinical outcomes. Epigenetic dysregulation, particularly involving the ubiquitin-like with phd and ring finger domains 1 (UHRF1), is increasingly recognized in cancer progression. However, the role of UHRF1 in OSCC and its regulation by cigarette smoking remains unclear. Therefore, the aim of this study was to investigate whether cigarette smoking influences UHRF1 expression in OSCC. Materials and methods UHRF1 expression was analyzed in OSCC tissues using publicly available Gene Expression Omnibus (GEO) datasets. Quantitative PCR and western blotting were employed to evaluate UHRF1 levels in OSCC cell lines. Functional assays, including colony formation, wound healing, and transwell invasion, were conducted following UHRF1 knockdown or overexpression. To investigate the impact of cigarette smoking on UHRF1 expression, cells were treated with cigarette smoke condensate (CSC) in a time-dependent manner. In vivo, a xenograft mouse model was used to assess the effect of CSC treatment on tumor growth and UHRF1 expression. Results As compared to normal tissue, UHRF1 was significantly overexpressed in OSCC tissues. Functional assays revealed that UHRF1 promotes OSCC cell proliferation, migration, and invasion. CSC treatment upregulated UHRF1 expression in vitro and enhanced tumor growth in vivo. Immunohistochemical analysis of xenograft tumors confirmed elevated UHRF1 expression following CSC exposure. Conclusion This study provides the first evidence that UHRF1 functions as an oncogenic driver in OSCC and may mediate smoking-induced tumorigenesis. These findings highlight UHRF1 as a potential biomarker and therapeutic target, particularly in smoking-associated OSCC.

Recommended Citation

Shieh, Yi-Shing; Wu, Jia-Rong; Yeh, Che-Ting; Chien, Chu-Yen; Chen, Ying-Chen; Huang, Tsai-Wang; Lin, Che-Yi; Hsieh, Alexander Cheng-Ting; and Hung, Yi-Jen (2025) "Ubiquitin-like with phd and ring finger domains 1 as a potential therapeutic target in smoking-associated oral squamous cell carcinoma," Journal of Dental Sciences: Vol. 20: Iss. 3, Article 68.
DOI: 10.1016/j.jds.2025.04.011
Available at: https://jds.ads.org.tw/journal/vol20/iss3/68