Dataset Information

The implications of N6-methyladenosine (m6A) modification in esophageal carcinoma.

ABSTRACT: Esophageal carcinoma (EC) is always diagnosed at advanced stage and its the mortality rate remains high. The patients usually miss the best opportunity for treatment because of non-specific symptoms and the survival rates are low. N6-methyladenosine (m6A) the predominant modification in eukaryotic messenger RNA(mRNA), serves vital roles in numerous bioprocess. This chemical modification is dynamic, reversible and consists of three regulators: m6A methyltransferases (writers), demethylases (erasers) and m6A-binding proteins (readers). Recently, a growing number of evidences have indicated relationships between m6A and EC. Whereas, lacking of cognition about the molecular mechanism of m6A modification in esophageal carcinoma. We will focus on the biological function roles of m6A modification in the tumorigenesis and development of EC. Recent studies showed that immunotherapy had a positive impact on EC. The relationship between m6A and immunotherapy in EC deserves further research and discussion. We will also discuss the potential clinical applications regarding diagnosis, treatment and prognosis of m6A modification for EC and provide perspectives for further studies.

SUBMITTER: He C

PROVIDER: S-EPMC10520198 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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The implications of N6-methyladenosine (m6A) modification in esophageal carcinoma.

He Cheng C Teng Xiao X Wang Luming L Ni Miaoqi M Zhu Linhai L Liu Jiacong J Lv Wang W Hu Jian J

Molecular biology reports 20230820 10

Esophageal carcinoma (EC) is always diagnosed at advanced stage and its the mortality rate remains high. The patients usually miss the best opportunity for treatment because of non-specific symptoms and the survival rates are low. N6-methyladenosine (m6A) the predominant modification in eukaryotic messenger RNA(mRNA), serves vital roles in numerous bioprocess. This chemical modification is dynamic, reversible and consists of three regulators: m6A methyltransferases (writers), demethylases (erase ...[more]

PMID: 37598390

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Project description:ObjectiveRecent research has suggested that m6A modification takes on critical significance to Neurodegeneration. As indicated by the genome-wide map of m6A mRNA, genes in Alzheimer's disease model achieved significant m6A methylation. This study aimed to investigate the hub gene and pathway of m6A modification in the pathogenesis of AD. Moreover, possible brain regions with higher gene expression levels and compounds exerting potential therapeutic effects were identified. Thus, this study can provide a novel idea to explore the treatment of AD.MethodsDifferential expression genes (DEGs) of GSE5281 and GSE48350 from the Gene Expression Omnibus (GEO) database were screened using the Limma package. Next, the enrichment analysis was conducted on the screened DEGs. Moreover, the functional annotation was given for N6-methyladenosine (m6A) modification gene. The protein-protein interaction network (PPI) analysis and the visualization analysis were conducted using STRING and Cytoscape. The hub gene was identified using CytoHubba. The expression levels of Hub genes in different regions of brain tissue were analyzed based on Human Protein Atlas (HPA) database and Bgee database. Subsequently, the candidate drugs targeting hub genes were screened using cMAP.ResultsA total of 42 m6A modified genes were identified in AD (20 up-regulated and 22 down-regulated genes). The above-described genes played a certain role in biological processes (e.g., retinoic acid, DNA damage response and cysteine-type endopeptidase activity), cellular components (e.g., mitochondrial protein complex), and molecular functions (e.g., RNA methyltransferase activity and ubiquitin protein ligase). KEGG results suggested that the above-mentioned genes were primarily involved in the Hippo signaling pathway of neurodegeneration disease. A total of 10 hub genes were screened using the protein-protein interaction network, and the expression of hub genes in different regions of human brain was studied. Furthermore, 10 compounds with potential therapeutic effects on AD were predicted.ConclusionThis study revealed the potential role of the m6A modification gene in Alzheimer's disease through the bioinformatics analysis. The biological changes may be correlated with retinoic acid, DNA damage response and cysteine-type endopeptidase activity, which may occur through Hippo signaling pathway. The hub genes (SOX2, KLF4, ITGB4, CD44, MSX1, YAP1, AQP1, EGR2, YWHAZ and TFAP2C) and potential drugs may provide novel research directions for future prognosis and precise treatment.

Project description:Background and objectiveHeart failure is the end-stage of various cardiovascular diseases. Recent progress in molecular biology has facilitated the understanding of the mechanisms of heart failure development at the molecular level. N6-adenosine methylation (m6A) is a post-transcriptional modification of RNA. Recent research work reported that m6A regulates gene expression and subsequently affects the activation of cell signaling pathways related to heart failure. Moreover, m6A regulators like methyltransferase-like 3 (METTL3) were reported to participate in myocardium hypertrophy. However, the current research work related to the role of m6A participating in the occurrence of heart failure is rare in some aspects like immune cell infiltration and diabetic heart diseases. Thus, it is reasonable to review the current achievements and provide further study orientation.MethodsWe searched related literature using the keywords: m6A AND heart failure in PubMed, Web of Science and Medline. The language was confined to English. The published year of searched literature ranged from 2012 to 2022. The searched results were put into Endnote software for management. Two authors investigated the searching terms and reviewed the full text of selected terms.Key content and findingsm6A and its regulators are involved in the metabolism of various types of RNAs. m6A modification can regulate various types of cell signaling pathways related to the heart failure via interaction with m6A regulators. m6A and its regulators broadly participate in the myocardium fibrosis, myocardium hypertrophy, myocardial cell apoptosis, and ischemic reperfusion injury. Specifically, m6A participates in the cell apoptosis via regulation of autophagy flux. However, the current research work does not have enough evidence to prove that m6A regulator played its specific effect on the target transcript via regulating the m6A level.Conclusionsm6A and its regulators participates in the progression of heart failure via modifying the RNA level. Future investigation of m6A should focus on the interaction between the m6A regulators and targeted transcript. Besides, the regulation role of m6A in immune cell infiltration and diabetic heart diseases should also be focused.

Project description:Aortic dissection (AD) develops pathological changes in the separation of the true and false aortic lumen, with high lethality. m6A methylation and oxidative stress have also been shown to be involved in the onset of AD. Through bioinformatics methods, three differentially expressed m6A regulators (YTHDC1, YTHDC2, and RBM15) were excavated from the GSE52093 dataset in the Gene Expression Omnibus (GEO) database, and functional enrichment analysis of the differentially expressed genes (DEGs) regulated by m6A regulators was performed. Then, the genes with oxidative stress-related functions among these genes were found. The protein interaction network of the oxidative stress-related genes and the competing endogenous RNA- (ceRNA-) miRNA-mRNA network were constructed. Among them, DHCR24, P4HB, and PDGFRA, which have m6A differences in AD samples, were selected as key genes. We also performed immune infiltration analysis, as well as cell-gene correlation analysis, on samples from the dataset. The results showed that YTHDC1 was positively correlated with macrophage M1 and negatively correlated with macrophage M2. Finally, we extracted AD and healthy aorta RNA and protein from human tissues that were taken from AD patients and patients who received heart transplants, performed quantitative real-time PCR (qRT-PCR) on YTHDC2 and RBM15, and performed qRT-PCR and western blot (WB) detection on YTHDC1 to verify their differences in AD. The mRNA and protein levels of YTHDC1 were consistent with the results of bioinformatics analysis and were downregulated in AD. Immunofluorescence (IF) was used to colocalize YTHDC1 and endothelial cell marker CD31. After knocking down YTHDC1 in human umbilical vein endothelial cells (HUVECs), reactive oxygen species (ROS) levels had a tendency to increase and the expression of peroxide dismutase SOD2 was decreased. This study provides assistance in discovering the role of m6A regulator YTHDC1 in AD. In particular, m6A modification participates in oxidative stress and jointly affects AD.

Dataset Information

The implications of N6-methyladenosine (m6A) modification in esophageal carcinoma.

Publications

The implications of N6-methyladenosine (m6A) modification in esophageal carcinoma.

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