Dataset Information

Consequences of aberrated DNA methylation in Colon Adenocarcinoma: a bioinformatic-based multi-approach.

ABSTRACT:

Introduction

The biology of colorectal cancer (CRC) is remained to be elucidated. Numerous genetic and epigenetic modifications are in concert to create and progress CRC. DNA methylation as a principal epigenetic factor has gained increased attention and could be utilized for biological studies. This study aims to find novel methylated and downregulated genes with a focus on HAND2 in CRC and decipher the biological consequences.

Material and method

Data on DNA methylation from GEO and SMART databases and the expression GEPIA2 database were downloaded. Afterward, a set of hypermethylated and downregulated genes in CRC was chosen by overlapping genes. Consequently, HAND2 was selected as a key gene for further investigation and confirmed with cell lines methylation and expression data. The functions of HAND2 were further analyzed using gene ontology analyses and the protein-protein interaction network.

Results

The methylation (p < 0.01) and expression (p < 0.01) of HAND2 are significantly varied in CRC compared to normal control. The correlation analysis (Pearson's correlation coefficient = -0.44, p = 6.6e-14) conveys that HAND2 significantly downregulated and has a reverse correlation with the methylation status of CpG islands. The biological process analysis of HAND2 target genes conveyed that disruption in HAND2 expression could dysregulate ERK1 and ERK2 signaling pathways.

Conclusion

Together, the findings showed that DNA hypermethylation of HAND2 was critical evidence in CRC. Further validation and prospective studies are needed to utilize HAND2 methylation as a promising biomarker.

SUBMITTER: Moradi A

PROVIDER: S-EPMC9706923 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Publications

Consequences of aberrated DNA methylation in Colon Adenocarcinoma: a bioinformatic-based multi-approach.

Moradi Arash A Shahsavari Milad M Gowdini Erfan E Mohammadian Kamal K Alizamir Aida A Khalilollahi Mohammad M Abgarmi Zahara Mohammadi ZM Ganji Shahla Mohammad SM

BMC genomic data 20221129 1

<h4>Introduction</h4>The biology of colorectal cancer (CRC) is remained to be elucidated. Numerous genetic and epigenetic modifications are in concert to create and progress CRC. DNA methylation as a principal epigenetic factor has gained increased attention and could be utilized for biological studies. This study aims to find novel methylated and downregulated genes with a focus on HAND2 in CRC and decipher the biological consequences.<h4>Material and method</h4>Data on DNA methylation from GEO ...[more]

PMID: 36443682

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Project description:Colorectal cancer is one of the 3 most common cancers worldwide. In this study, a weighted network-based analysis method was proposed to explore the pathological mechanisms and prognostic targets of rectal adenocarcinoma (READ) at the deoxyribonucleic acid (DNA) methylation level. In this study, we downloaded clinical information and DNA methylation data from The Cancer Genome Atlas database. Differentially methylated gene analysis was used to identify the differential methylated genes in READ. Canonical correlation analysis was used to construct the weighted gene regulatory network for READ. Multilevel analysis and association analyses between gene modules and clinical information were used to mine key modules related to tumor metastasis evaluation. Genetic significance analysis was used to identify methylation sites in key modules. Finally, the importance of these methylation sites was confirmed using survival analysis. DNA methylation datasets from 90 cancer tissue samples and 6 paracancerous tissue samples were selected. A weighted gene regulatory network was constructed, and a multilevel algorithm was used to divide the gene co-expression network into 20 modules. From gene ontology enrichment analysis, characteristic M was related to biological processes such as the chemotaxis of fibroblast growth factors and the activation and regulation of immune cells etc and characteristic N was associated with the regulation of cytoskeleton formation, mainly microtubules and flagella, regulation of synapses, and regulation of cell mitosis. Based on the results of survival analysis, 7 key methylation sites were found closely correlated to the survival rate of READ, such as cg04441191 (microtubule-associated protein 4 [MAP4]), cg05658717 (KSR2), cg09622330 (GRIN2A), cg10698404 (YWHAG), cg17047993 (SPAG9), cg24504843 (CEP135), and cg24531267 (CEP250). Mutational and transcriptomic level studies revealed significant differences in DNA methylation, single nucleotide polymorphism, and transcript levels between YWHAG and MAP4 in normal tissues compared to tumor tissues, and differential expression of the 2 proteins in immunohistochemistry. Therefore, potential targeting drugs were screened for these 2 proteins for molecular docking, and artenimol was found to bind to MAP4 protein and 27-hydroxycholesterol to YWHAG. Our study found that key methylation sites played an important role in tumor metastasis and were associated with the prognosis of READ. Mutations and methylation may jointly regulate the transcription and translation of related genes, which in turn affect cancer progression. This may provide some new potential therapeutic targets and thoughts for the prognosis of READ.

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Dataset Information

Consequences of aberrated DNA methylation in Colon Adenocarcinoma: a bioinformatic-based multi-approach.

Introduction

Material and method

Results

Conclusion

Publications

Consequences of aberrated DNA methylation in Colon Adenocarcinoma: a bioinformatic-based multi-approach.

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