Genome-wide DNA methylation profiling reveals distinct epigenetic features in nasopharyngeal cancer stem cells

Cancer stem cells (CSCs) contribute greatly to the initiation, progression, metastasis, and drug resistance of cancers. Nasopharyngeal carcinoma (NPC) is a malignant tumor that has distinct ethnic and geographical distributions and could be related to epigenetic alterations. Aberrant DNA methylation, an important type of epigenetic disorder, has long been known to be important in the pathogenesis of NPC. However, DNA methylation alterations in NPC CSCs remain unresolved. In this study, the genome-wide DNA methylation profiles of NPC cells (CNE2 and C666-1) were compared with those of their corresponding CSCs (CNE2 CSCs and C666-1 CSCs) to determine the distinct DNA methylation patterns of NPC CSCs. Compared with that of CNE2 cells, which are Epstein–Barr virus (EBV)-negative NPC cells, the DNA of CNE2 CSCs is highly hypomethylated. In contrast, the DNA of EBV-harboring CSCs (C666-1 CSCs) had more hypermethylated sites than that of C666-1. The differentially methylated genes (DMGs) in CNE2 CSCs compared with those in CNE2 cells were enriched mainly in metabolism-related terms, and UGT1A9, UGT1A3, and UGT1A4 were identified as hub genes. However, the DMGs in C666-1 CSCs compared with those in C666-1 cells were enriched mainly in cancer-associated signaling pathways and virus infection-associated terms, and the hub genes were MACF1, ACTA1, and TP63. Our work revealed distinct methylation patterns in NPC CSCs, which is beneficial for obtaining a deeper understanding of the pathogenesis of NPC.