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

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.