口腔疾病防治 ›› 2021, Vol. 29 ›› Issue (10): 677-683.DOI: 10.12016/j.issn.2096-1456.2021.10.005

• 基础研究 • 上一篇    下一篇

DNA甲基化激活磷酸肌醇代谢在口腔白斑癌变中的意义

王广超(),刘丽骏,蒋伟文()   

  1. 上海交通大学医学院附属第九人民医院口腔黏膜病科,上海交通大学口腔医学院,国家口腔疾病临床研究中心,上海市口腔医学重点实验室,上海市口腔医学研究所,上海(200011)
  • 收稿日期:2021-01-30 修回日期:2021-05-01 出版日期:2021-10-20 发布日期:2021-06-23
  • 通讯作者: 蒋伟文
  • 作者简介:王广超,硕士研究生,Email: wgc119@foxmail.com
  • 基金资助:
    国家自然科学基金项目(81671036)

Significance of phosphoinositol metabolism by DNA methylation may contribute in oral leukoplakia carcinogenesis

WANG Guangchao(),LIU Lijun,JIANG Weiwen()   

  1. Department of Oral Mucosal Diseases, Shanghai Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai 200011, China
  • Received:2021-01-30 Revised:2021-05-01 Online:2021-10-20 Published:2021-06-23
  • Contact: Weiwen JIANG
  • Supported by:
    National Natural Science Foundation of China(81671036)

摘要:

目的 探讨DNA甲基化修饰在口腔白斑癌变中的作用。方法 选取40例口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)组织和28例口腔白斑(oral leukoplakia,OLK)组织以及40例健康口腔黏膜组织进行DNA甲基化检测。下载GEO(Gene Expression Omnibus)数据库中OSCC、OLK和健康口腔黏膜的表达谱数据。分别对DNA甲基化数据和表达谱数据进行重复性比对,对DNA甲基化数据进行差异分析以及对相应表达谱数据进行IPA分析(Ingenuity Pathway Analysis)。结果 数据分析结果显示DNA甲基化具有更大的灵活性和不稳定性。IPA通路分析表明,OLK差异甲基化位点相关基因主要富集在细胞运动和分化过程。OSCC差异甲基化位点相关基因主要富集在细胞增殖、迁移、氧化调节、抗凋亡等过程。OLK和OSCC差异甲基化位点相关基因共同富集于磷酸肌醇代谢过程和磷脂酶C信号通路。结论 DNA甲基化改变参与口腔鳞癌形成,磷酸肌醇代谢激活可能促使口腔白斑癌变。

关键词: 口腔白斑, 口腔鳞状细胞癌, 表观遗传学, DNA甲基化, 肌醇, 磷酸肌醇, 代谢, 磷脂酶C, 炎症, 钙信号

Abstract:

Objective To study the role of DNA methylation in oral leukoplakia carcinogenesis. Methods DNA methylation was detected in forty cases of oral squamous cell carcinoma (OSCC), twenty-eight cases of oral leukoplakia (OLK) and forty cases of healthy oral mucosa. Download the expression profile data of OSCC, OLK and healthy oral mucosa from Gene Expression Omnibus (GEO) database. DNA methylation data and expression profile data were compared for repeatability, DNA methylation data for difference analysis and corresponding expression profile data for IPA pathway analysis. Results The data analysis showed that DNA methylation had greater flexibility and instability. Ingenuity Pathway Analysis (IPA) analysis showed that genes related to OLK differential methylation sites were mainly concentrated in the process of cell movement and differentiation. Genes related to differential methylation sites of OSCC are mainly enriched in cell proliferation, migration, oxidation regulation, and anti-apoptosis processes. The genes associated with OLK and OSCC differential methylation sites are co-enriched in phosphoinositol metabolism and phospholipase C signaling pathway. Conclusion DNA methylation is involved in the formation of oral squamous cell carcinoma, and the activation of phosphoinositol metabolism may promote oral leukinoma.

Key words: oral leukoplakia, oral squamous cell carcinoma, epigenetics, DNA methylation, inositol, phosphoinositol, metabolism, phospholipase C, inflammation, calcium signal

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