A Comprehensive Analysis of the Role of PAX9 in Head and Neck Squamous Cell Carcinoma.

IF 2.2 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Current molecular medicine Pub Date : 2025-01-15 DOI:10.2174/0115665240328109241205084841
Lang Zeng, Wenjing Yun, Wen-Long Luo
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Abstract

Background: Paired box 9 (PAX9) has been linked to several human disorders; however, its relevance in Head And Neck Squamous Cell Carcinoma (HNSCC) remains unknown.

Methods: The difference in PAX9 mRNA expression in pan-cancer was analyzed utilizing The Cancer Genome Atlas (TCGA), and the level of PAX9 protein expression across various types of cancer was assessed utilizing the Human Protein Atlas (HPA) and UALCAN databases, as well as the cellular localization of PAX9. UALCAN studied the methylation levels of PAX9 in pan-cancer. The predictive significance of PAX9 in pan-cancer was assessed utilizing the Kaplan-Meier Plotter website. Functional enrichment analysis was carried out with the "cluster Profiler" program. By employing CCK8 and colony formation methods, the influence of PAX9 on the growth of HNSCC cells was evaluated. By conducting a transwell experiment, we assessed the influence of PAX9 on the migration of HNSCC cells. Western blotting was used to determine the levels of Bax and Bcl-2, two proteins involved in the regulation of apoptosis. A nude mouse model was established to study the impact of PAX9 overexpression on the growth of subcutaneous HNSCC tumors.

Results: In HNSCC, the expression of PAX9 was found to be low, while levels of promoter methylation rose considerably. Low PAX9 expression has been linked to a decrease in overall survival (OS) rates among individuals with HNSCC. Furthermore, overexpressing the PAX9 gene decreased HNSCC cell proliferation, migration, and invasion while boosting apoptosis rates.

Conclusion: The abnormal expression of PAX9 is linked to various cancers. In HNSCC, PAX9 is a potential tumor suppressor, inhibiting tumor invasion and migration. The results reveal a potentially significant new therapeutic target for HNSCC.

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PAX9在头颈部鳞状细胞癌中作用的综合分析
背景:配对框9 (PAX9)与几种人类疾病有关;然而,其与头颈部鳞状细胞癌(HNSCC)的相关性尚不清楚。方法:利用The Cancer Genome Atlas (TCGA)分析PAX9 mRNA在泛癌组织中的表达差异,利用Human protein Atlas (HPA)和UALCAN数据库评估PAX9蛋白在不同类型癌症中的表达水平,以及PAX9的细胞定位。UALCAN研究了泛癌组织中PAX9的甲基化水平。利用Kaplan-Meier Plotter网站评估PAX9在泛癌中的预测意义。使用“cluster Profiler”程序进行功能富集分析。采用CCK8和集落形成法,评估PAX9对HNSCC细胞生长的影响。通过transwell实验,我们评估了PAX9对HNSCC细胞迁移的影响。Western blotting检测参与细胞凋亡调控的两种蛋白Bax和Bcl-2的水平。建立裸鼠模型,研究PAX9过表达对HNSCC皮下肿瘤生长的影响。结果:在HNSCC中,PAX9的表达较低,而启动子甲基化水平明显升高。低PAX9表达与HNSCC患者总生存率(OS)的降低有关。此外,过表达PAX9基因可降低HNSCC细胞的增殖、迁移和侵袭,同时提高细胞凋亡率。结论:PAX9的异常表达与多种癌症有关。在HNSCC中,PAX9是一种潜在的肿瘤抑制因子,可以抑制肿瘤的侵袭和迁移。结果揭示了一个潜在的重要的新治疗靶点HNSCC。
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来源期刊
Current molecular medicine
Current molecular medicine 医学-医学:研究与实验
CiteScore
5.00
自引率
4.00%
发文量
141
审稿时长
4-8 weeks
期刊介绍: Current Molecular Medicine is an interdisciplinary journal focused on providing the readership with current and comprehensive reviews/ mini-reviews, original research articles, short communications/letters and drug clinical trial studies on fundamental molecular mechanisms of disease pathogenesis, the development of molecular-diagnosis and/or novel approaches to rational treatment. The reviews should be of significant interest to basic researchers and clinical investigators in molecular medicine. Periodically the journal invites guest editors to devote an issue on a basic research area that shows promise to advance our understanding of the molecular mechanism(s) of a disease or has potential for clinical applications.
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