Adhikari Bhoj Raj, Uehara Osamu, Matsuoka Hirofumi, Takai Rie, Harada Fumiya, Utsunomiya Masafumi, Chujo Takatoshi, Morikawa Tetsuro, Shakya Mamata, Yoshida Koki, Sato Jun, Arakawa Toshiya, Nishimura Michiko, Nagayasu Hiroki, Chiba Itsuo, Abiko Yoshihiro
Division of Oral Medicine and Pathology, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan.
Division of Disease Control and Molecular Epidemiology, Department of Oral Growth and Development, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan.
Med Mol Morphol. 2017 Sep;50(3):155-160. doi: 10.1007/s00795-017-0156-9. Epub 2017 Mar 16.
Carcinoma follows a course of multiple changes that are affected by several important factors, with epigenetic silencing of the promoter gene being one of them. A series of studies have suggested that epigenetic changes in the anti-aging gene Klotho may be one of the emerging areas of concern in the study of carcinogenesis. We hypothesized that epigenetic silencing of Klotho due to hypermethylation of DNMT3a may be one of the causes of carcinoma in the oral and maxillofacial region. In this study, we analyzed the immunohistochemical expressions of Klotho and DNMT3a in tissues obtained from oral dysplasia and oral squamous cell carcinoma. Our results showed increased immune expression of DNMT3a, and decreased expression of Klotho in cells of the cancer tissues when compared with those in the dysplasia and healthy control samples. Chi-square tests complemented by adjusted residual analysis revealed significantly higher number of Klotho-positive and DNMT3a-negative cases in healthy controls, Klotho-negative and DNMT3a-negative cases in ODL, and Klotho-negative and DNMT3a-positive cases in OSCC when compared with the other types among the three groups (X = 46.66, p < 0.001). Thus, downregulation of Klotho may be associated with the overexpression of DNMT3a in cancer tissues.
癌症的发生过程伴随着多种变化，这些变化受几个重要因素影响，其中启动子基因的表观遗传沉默是因素之一。一系列研究表明，抗衰老基因Klotho的表观遗传变化可能是癌症发生机制研究中一个新出现的关注领域。我们推测，由于DNMT3a的高甲基化导致Klotho的表观遗传沉默可能是口腔颌面部癌症的病因之一。在本研究中，我们分析了从口腔发育异常和口腔鳞状细胞癌组织中获取的Klotho和DNMT3a的免疫组化表达。我们的结果显示，与发育异常和健康对照样本相比，癌组织细胞中DNMT3a的免疫表达增加，而Klotho的表达降低。卡方检验辅以调整残差分析显示，与三组中的其他类型相比，健康对照中Klotho阳性和DNMT3a阴性病例数显著更高，口腔发育异常中Klotho阴性和DNMT3a阴性病例数显著更高，口腔鳞状细胞癌中Klotho阴性和DNMT3a阳性病例数显著更高（X = 46.66，p < 0.001）。因此，Klotho的下调可能与癌组织中DNMT3a的过表达有关。
