Pan-cancer analysis of m5C regulator genes reveals consistent epigenetic landscape changes in multiple cancers

Yuting He,Wenzhi Guo,Menggang Zhang,Xiao Yu

doi:10.1186/s12957-021-02342-y

Yuting He, Wenzhi Guo + Show 2 more

Open Access

https://doi.org/10.1186/s12957-021-02342-y

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Abstract

Background5-Methylcytosine (m5C) is a reversible modification to both DNA and various cellular RNAs. However, its roles in developing human cancers are poorly understood, including the effects of mutant m5C regulators and the outcomes of modified nucleobases in RNAs.MethodsBased on The Cancer Genome Atlas (TCGA) database, we uncovered that mutations and copy number variations (CNVs) of m5C regulatory genes were significantly correlated across many cancer types. We then assessed the correlation between the expression of individual m5C regulators and the activity of related hallmark pathways of cancers.ResultsAfter validating m5C regulators’ expression based on their contributions to cancer development and progression, we observed their upregulation within tumor-specific processes. Notably, our research connected aberrant alterations to m5C regulatory genes with poor clinical outcomes among various tumors that may drive cancer pathogenesis and/or survival.ConclusionOur results offered strong evidence and clinical implications for the involvement of m5C regulators.

Highlights

Cancers have become the second life-threatening malignancies, which contribute to almost 18.1 million people occurred and 9.6 million death globally in 2018 [1]
Study workflow We downloaded fragments of kilobase transcripts based on fragments per kilobase of transcript per million (FPKM) gene expression from The Cancer Genome Atlas (TCGA, https://www.cancer.gov/) dataset among 33 different cancer types. m5C regulator patterns were investigated in 5480 samples among 33 different cancer types, including somatic mutations, copy number variations (CNVs), gene expression, and RNA-seq data (Fig. 1B)
Results m5C regulators identification and its genomic extensive genetic changes In this study, we identified 13 m5C regulators, as shown in Fig. 1A, eleven writers (NSUN1-7, DNMT1, DNMT2, DNMT3A, and DNMT3B), one eraser (TET2), and one reader (ALYREF)

Summary

Introduction

Cancers have become the second life-threatening malignancies, which contribute to almost 18.1 million people occurred and 9.6 million death globally in 2018 [1]. Growing evidence demonstrated that genomic instability [4, 5], oncogene activation, aberrant methylation modifications, alterations in epigenetic changes [6,7,8], aberrant expression of microRNAs [9], and alterations of signaling pathways [10,11,12]. The 5-methylcytosine (m5C), N6-methyladenine (m6A), and N1-methyladenosine (m1A) have become the most common types of epigenetic modifications in eukaryotes [13]. Emerging evidence has demonstrated that m5C modification has the potential to serve as novel epigenetic markers with remarkable biological significance in biological processes [18,19,20]. m5C regulators contain writers, erasers, and readers, which function as common epigenetic modification and contribute to premRNA splicing, gene expression, gene silencing, nuclear export, genomic maintenance, and translation initiation Emerging evidence has demonstrated that m5C modification has the potential to serve as novel epigenetic markers with remarkable biological significance in biological processes [18,19,20]. m5C modification distributes in different types of RNAs and DNAs [21,22,23]. m5C modifications can even modify the destiny of cancer cells [24]. m5C regulators contain writers, erasers, and readers, which function as common epigenetic modification and contribute to premRNA splicing, gene expression, gene silencing, nuclear export, genomic maintenance, and translation initiation

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