Identification of Expression Patterns and Potential Prognostic Significance of m5C-Related Regulators in Head and Neck Squamous Cell Carcinoma

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.

NSUN2 Promotes Tumor Progression and Regulates Immune Infiltration in Nasopharyngeal Carcinoma

“…Among them, 5-methylcytosine (m5C), one of the most important types of post-transcriptional modifications, was first found in tRNAs and rRNA, and has recently been found in mRNA and noncoding RNA (5). Similar to the N6-methyladenosine (m6A) m o d i fi c a t i o n , t h e m 5 C m o d i fi c a t i o n h a s i t s o w n methyltransferase "Writer," demethylase "Eraser," and binding protein "Reader" (5,6). NSUN2, a methyltransferase of m5C, is responsible for the m5C modification in the mRNA of mammals (7).…”

The cuproptosis-related signature predicts prognosis and indicates immune microenvironment in breast cancer

“…These results showed the significance of CRRs in regulating the occurrence, development and treatment of tumors. Consensus Clustering is a common method of classifying cancer subtypes (Zhang et al, 2020;Wu et al, 2021c;Han et al, 2021). We performed consensus clustering with the five prognostic CRRs in TCGA-BRCA data and two distinct cuproptosis-clusters were identified.…”

Aberrations of DNA methylation in cancer

“…Было показано, что повышенный уровень экспрессии DNMT1 в тканях карциномы шейки матки статистически значимо коррелирует с худшим прогнозом течения заболевания [76]. Нарушение регуляции DNMT1, а также повышенная экспрессия генов DNMT3a и DNMT3b связаны с прогрессированием плоскоклеточного рака головы и шеи у пожилых пациентов [77,78]. Согласно данным S. L. Zhao и соавт., при раке пищевода гиперэкспрессия DNMT1 обусловливает подавление активности генов супрессоров опухолей, а также коррелирует с метастазированием в лимфатические узлы [79].…”

“…In vivo (mice), in vitro (MCF7, T47D, ZR75.1, BT474, MDAMB361, MDA-MB-231, MDAMB453, MDAMB468, BT20) [86] In vitro (MCF- In silico (n = 501) [78] In silico (n = 520) [ In vitro (первичная культура E-PZ-231)…”