Wu Jia-Rong, Yeh Che-Ting, Chien Chu-Yen, Chen Ying-Chen, Huang Tsai-Wang, Lin Che-Yi, Cheng-Ting Hsieh Alexander, Hung Yi-Jen, Shieh Yi-Shing
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
School of Dentistry, National Defense Medical Center, Taipei, Taiwan.
J Dent Sci. 2025 Jul;20(3):1772-1781. doi: 10.1016/j.jds.2025.04.011. Epub 2025 Apr 24.
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.
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.
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.
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.
背景/目的：口腔鳞状细胞癌（OSCC）是一种常见且侵袭性强的恶性肿瘤，临床预后较差。表观遗传失调，尤其是涉及含植物同源结构域和指环结构域1（UHRF1）的类泛素化过程，在癌症进展中越来越受到关注。然而，UHRF1在OSCC中的作用及其受吸烟的调控仍不清楚。因此，本研究的目的是探讨吸烟是否会影响OSCC中UHRF1的表达。
利用公开的基因表达综合数据库（GEO）数据集分析OSCC组织中UHRF1的表达。采用定量PCR和蛋白质免疫印迹法评估OSCC细胞系中UHRF1的水平。在UHRF1基因敲低或过表达后进行功能实验，包括集落形成、伤口愈合和Transwell侵袭实验。为了研究吸烟对UHRF1表达的影响，细胞用香烟烟雾冷凝物（CSC）进行时间依赖性处理。在体内，使用异种移植小鼠模型评估CSC处理对肿瘤生长和UHRF1表达的影响。
与正常组织相比，UHRF1在OSCC组织中显著过表达。功能实验表明，UHRF1促进OSCC细胞增殖、迁移和侵袭。CSC处理在体外上调UHRF1表达，在体内增强肿瘤生长。对异种移植肿瘤的免疫组织化学分析证实CSC暴露后UHRF1表达升高。
本研究首次证明UHRF1在OSCC中作为致癌驱动因子发挥作用，并可能介导吸烟诱导的肿瘤发生。这些发现突出了UHRF1作为潜在生物标志物和治疗靶点的作用，尤其是在与吸烟相关的OSCC中。
