Dataset Information

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.

SUBMITTER: He Y

PROVIDER: S-EPMC8323224 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Publications

Pan-cancer analysis of m<sup>5</sup>C regulator genes reveals consistent epigenetic landscape changes in multiple cancers.

He Yuting Y Yu Xiao X Zhang Menggang M Guo Wenzhi W

World journal of surgical oncology 20210729 1

<h4>Background</h4>5-Methylcytosine (m<sup>5</sup>C) 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 m<sup>5</sup>C regulators and the outcomes of modified nucleobases in RNAs.<h4>Methods</h4>Based on The Cancer Genome Atlas (TCGA) database, we uncovered that mutations and copy number variations (CNVs) of m<sup>5</sup>C regulatory genes were significantly correlated across ma ...[more]

PMID: 34325709

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Project description:IntroductionThe HIV regulatory protein Tat enhances viral transcription and also modifies host gene expression, affecting cell functions like cell cycle and apoptosis. Residual expression of Tat protein is detected in blood and other tissues even under antiretroviral treatment. Cohort studies have indicated that, despite virologic suppression, people with HIV (PWH) are at increased risk of comorbidities linked to chronic inflammation, accelerated immune ageing, and cellular senescence, sometimes associated with abnormal genomic methylation patterns. We analysed whether Tat influences DNA methylation and subsequently impacts the transcriptional signature, contributing to inflammation and accelerated ageing.MethodsWe transfected Jurkat cells with full-length Tat (Tat101), Tat's first exon (Tat72), or an empty vector (TetOFF). We assessed DNA methylation modifications via the Infinium MethylationEPIC array, and we evaluated transcriptomic alterations through RNA-Seq. Methylation levels in gene promoters or body regions were correlated to their expression data, and subsequently, we performed an overrepresentation analysis to identify the biological terms containing differentially methylated and expressed genes.ResultsTat101 expression caused significant hyper- and hypomethylation changes at individual CpG sites, resulting in slightly global DNA hypermethylation. Methylation changes at gene promoters and bodies resulted in altered gene expression, specifically regulating gene transcription in 5.1% of differentially expressed genes (DEGs) in Tat101- expressing cells. In contrast, Tat72 had a minimal impact on this epigenetic process. The observed differentially methylated and expressed genes were involved in inflammatory responses, lipid antigen presentation, and apoptosis.DiscussionTat expression in HIV infection may constitute a key epigenetic modelling actor that contributes to HIV pathogenesis and chronic inflammation. Clinical interventions targeting Tat blockade may reduce chronic inflammation and cellular senescence related to HIV infection comorbidities.

Project description:ObjectivesCancer has emerged as a global issue in terms of public health care and treatment. The significance of calcyclin binding protein (CACYBP) in various neoplasms suggests that it may serve as a novel biomarker for numerous types of human tumors.MethodsOur research investigated the differences in CACYBP expression between cancer tissues and normal tissues using a total of 18,787 samples from multiple centers. To explore the prognostic factor of CACYBP in cancers, we utilized Cox regression analysis and Kaplan-Meier curves. We also conducted Spearman's rank correlation analyses to determine the associations of CACYBP expression with the immune microenvironment, etc. Additionally, we applied gene set enrichment analysis to explore the underlying mechanisms of CACYBP in cancers. A partial validation of CacyBP expression in cancer tissues was performed through lung adenocarcinoma samples using Western blotting and paired t-test.ResultsCompared to normal tissues, CACYBP exhibited high expression levels in 14 cancer types, including breast invasive carcinoma, and low expression levels in six cancers, including glioblastoma multiforme (P < 0.05). CACYBP expression was found to be significantly associated with the prognosis of 13 cancers, including adrenocortical carcinoma (P < 0.05). CACYBP demonstrated a robust ability to distinguish 15 cancers, including cholangiocarcinoma, from their control samples (area under the curve > 0.8). Furthermore, CACYBP expression was correlated with tumor mutational burden, microsatellite instability, and immune infiltration levels, indicating its potential as an exciting target for cancer treatment. CACYBP may exert its effects on several signaling pathways, including cytokine-cytokine receptor interaction, in various cancers. Compared with paired adjacent specimens, the expression level of CacyBP protein was up-regulated in lung adenocarcinoma specimens (P < 0.05), partially validating the increased expression of CACYBP in cancers.ConclusionsCACYBP has the potential to serve as a novel prognostic and predictive marker for multiple human cancers.

Dataset Information

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

Background

Methods

Results

Conclusion

Publications

Pan-cancer analysis of m<sup>5</sup>C regulator genes reveals consistent epigenetic landscape changes in multiple cancers.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

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

Background

Methods

Results

Conclusion

Publications

Pan-cancer analysis of m<sup>5</sup>C regulator genes reveals consistent epigenetic landscape changes in multiple cancers.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

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