Abstract
5-Methylcytosine (m5C) methylation is a major epigenetic technique of RNA modification and is dynamically mediated by m5C “writers,” “erasers,” and “readers.” m5C RNA modification and its regulators are implicated in the onset and development of many tumors, but their roles in head and neck squamous cell carcinoma (HNSCC) have not yet been completely elucidated. In this study, we examined expression patterns of core m5C regulators in the publicly available HNSCC cohort via bioinformatic methods. The differentially expressed m5C regulators could divide the HNSCC cohort into four subgroups with distinct prognostic characteristics. Furthermore, a three-gene expression signature model, comprised of NSUN5, DNMT1, and DNMT3A, was established to identify individuals with a high or low risk of HNSCC. To explore the underlying mechanism in the prognosis of HNSCC, screening of differentially expressed genes, followed by the analysis of functional and pathway enrichment, from individuals with high- or low-risk HNSCC was performed. The results revealed a critical role for m5C RNA modification in two aspects of HNSCC: (1) dynamic m5C modification contributes to the regulation of HNSCC progression and (2) expression patterns of NSUN5, DNMT1, and DNMT3A help to predict the prognosis of HNSCC.
Highlights
According to the most recent report, head and neck squamous cell carcinoma (HNSCC) is a relatively lethal type of cancer, and HNSCC ranks among the top six in terms of incidence and mortality, seriously threatening public health and the quality of life of patients with HNSCC worldwide [1]
Expression levels of the individual m5C RNA methylation catalase in HNSCC and control samples are presented in the heat map (Figure 2A)
Of these 14 genes, the majority of writers (NOP2, NSUN2, NSUN3, NSUN4, NSUN5, NSUN6, DNMT3A, DNMT3B, and DNMT1) were more substantially upregulated in the HNSCC samples compared with normal tissues, with the exception of NSUN7, which showed an opposite expression trend with the other 9 m5C writers (p < 0.05)
Summary
According to the most recent report, head and neck squamous cell carcinoma (HNSCC) is a relatively lethal type of cancer, and HNSCC ranks among the top six in terms of incidence and mortality, seriously threatening public health and the quality of life of patients with HNSCC worldwide [1]. HNSCC therapy has undergone a significant change in recent years with the Profiles of m5C in HNSCC development of precision medicines, such as bevacizumab, against vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) based on the special gene expression signature, and prognostic outcomes in HNSCC [3,4,5]. Increasing knowledge has brought into focus the features of several macromolecules (protein, RNA, DNA, and sugar) that are involved in tumorigenesis and progression, especially in epigenetic modifications; and the value of these features as prognostic indicators and potential therapeutic targets has been gradually recognized [6,7,8].
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