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

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