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

Abstract

Background 5-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. Methods Based 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. Results After 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. Conclusion Our results offered strong evidence and clinical implications for the involvement of m5C regulators.

Expression and Functional Roles of Eukaryotic Initiation Factor 4A Family Proteins in Human Cancers

“…The patient information was similar to that in a previous study (He et al, 2021). As shown in Figure 3, eIF4A1 was significantly overexpressed in tumor tissues compared to normal control tissues, including breast invasive carcinoma (BRCA), cholangiocarcinoma (CHOL), colon adenocarcinoma (COAD), esophageal carcinoma (ESCA), head and neck squamous cell carcinoma (HNSC), kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), prostate adenocarcinoma (PRAD), rectum adenocarcinoma (READ), stomach adenocarcinoma (STAD), and uterine corpus endometrial carcinoma (UCEC).…”

Construction of an individualized clinical prognostic index based on ubiquitination-associated lncRNA in clear cell renal cell carcinoma patients

“…However, this risk signature included the differential expressed genes (DEGs) as well as autophagy-related genes (ARGs) for regression analysis, and some ARGs did not reach DEGs criteria, which may contribute to the potential bias for this risk signature. Additionally, ubiquitination was considered to control multiple steps of autophagy, essential for autophagy flux regulation in a variety of signaling pathways [ 30 – 32 ]. DEGs related to ubiquitination may provide a superior prediction value than those related to ARGs.…”

Advances in RNA Epigenetic Modifications in Hepatocellular Carcinoma and Potential Targeted Intervention Strategies

“…In addition, some studies have also found thousands of m5C methylation peaks in circRNAs of HCC tissue, and the number and distribution of these methylation peaks are significant between HCC and adjacent tissues (He et al, 2020b). Whole chromosome level analysis showed a significantly different distribution of m5C-methylated circRNA in multiple chromosomes between cancer and adjacent tissues, especially the X chromosome, suggesting that m5C changes extensively in HCC tissues and may affect HCC phenotypes through multiple avenues (Torsin et al, 2021).…”

“…To date, research on m5C in HCC has made some progress, as shown in Figure 2B. Many studies have shown that the high expression of almost all m5C regulators is significantly related to the shorter overall survival period of HCC patients except for NSUN7, suggesting that the dysfunction of m5C regulators has a strong impact on HCC progression (He et al, 2021). Since then, a study used clinical information from the TCGA database to assess m5C regulator alterations and the survival rate in patients and found that the p-value of the NSUN5 and ALYREF genes in HCC is less than 0.05, as well as the significant difference in the NSUN6 gene, which provides an important basis for exploring m5C regulators as potential therapeutic targets for HCC (Song et al, 2021).…”