Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 701401, Taiwan.
Institute of Oral Medicine, Department of Dentistry, College of Medicine, National Cheng Kung University, Tainan 701401, Taiwan.
Int J Mol Sci. 2022 Apr 19;23(9):4495. doi: 10.3390/ijms23094495.
Oral squamous cell carcinoma (OSCC) accounts for over 90% of oral cancers and causes considerable morbidity and mortality. Epigenetic deregulation is a common mechanism underlying carcinogenesis. DNA methylation deregulation is the epigenetic change observed during the transformation of normal cells to precancerous and eventually cancer cells. This study investigated the DNA methylation patterns of during the development of OSCC. Bisulfite genomic DNA sequencing was performed to determine the methylation level. OSCC animal models were established to examine changes in PTK6 expression in the different stages of OSCC development. The DNA methylation of was decreased during the development of OSCC. The mRNA and protein expression of PTK6 was increased in OSCC cell lines compared with human normal oral keratinocytes. In mice, the methylation level of decreased after treatment with 4-nitroquinoline 1-oxide and arecoline, and the mRNA and protein expression of PTK6 was increased. hypomethylation can be a diagnostic marker of OSCC. Upregulation of PTK6 promoted the proliferation, migration, and invasion of OSCC cells. PTK6 promoted carcinogenesis and metastasis by increasing STAT3 phosphorylation and ZEB1 expression. The epigenetic deregulation of can serve as a biomarker for the early detection of OSCC and as a treatment target.
口腔鳞状细胞癌 (OSCC) 占口腔癌的 90%以上，导致相当高的发病率和死亡率。表观遗传失调是癌症发生的常见机制。DNA 甲基化失调是正常细胞向癌前病变和最终癌变过程中观察到的表观遗传变化。本研究探讨了 OSCC 发生过程中 的 DNA 甲基化模式。亚硫酸氢盐基因组 DNA 测序用于确定 的甲基化水平。建立 OSCC 动物模型，以研究 PTK6 在 OSCC 发展的不同阶段表达的变化。在 OSCC 的发展过程中， 的 DNA 甲基化减少。与正常人正常口腔角质形成细胞相比，PTK6 在 OSCC 细胞系中的 mRNA 和蛋白表达增加。在小鼠中，在用 4-硝基喹啉 1-氧化物和槟榔碱处理后， 的甲基化水平降低，PTK6 的 mRNA 和蛋白表达增加。 低甲基化可能是 OSCC 的诊断标志物。PTK6 的上调促进了 OSCC 细胞的增殖、迁移和侵袭。PTK6 通过增加 STAT3 磷酸化和 ZEB1 表达促进致癌作用和转移。 的表观遗传失调可作为 OSCC 早期检测的生物标志物，并可作为治疗靶点。
