Correlation of DNA methylation of DNMT3A and TET2 with oral squamous cell carcinoma

Abstract

Oral squamous cell carcinoma (OSCC) is the sixth most common malignancy worldwide. Abnormal epigenetic modifications, including DNA methylation, are hallmarks of cancer and implicated in the development of various tumors. DNA methylation is catalyzed by the DNA methyltransferase and ten-eleven translocation dioxygenase families, with DNMT3A and TET2 being the most widely studied members, respectively. The correlation of methylation β values and clinical features was conducted in patients with OSCC in The Cancer Genome Atlas database. DNA methylation and protein expression levels of DNMT3A and TET2 in tissues were analyzed with methylation-specific polymerase chain reaction (MSP) and western blotting. To evaluate the effects of DNMT3A and TET2 on the biological characteristics of OSCC, cell proliferation was assessed with 5-ethynyl-2'-deoxyuridine, and cell migration capacity was quantified with wound healing and transwell assays. A survival analysis was performed with the Kaplan–Meier approach. The correlation between different methylation β values and clinical features was revealed. MSP revealed varying methylation degrees of DNMT3A and TET2 in OSCC tissues. Furthermore, western blotting showed that the protein expression levels were significantly different in cancer and surrounding healthy tissue samples. In vitro experiments demonstrated that DNMT3A knockdown and TET2 overexpression could inhibit the proliferation and migration of OSCC. Survival analysis revealed that patients with high DNMT3A methylation levels showed higher survival rates.