Genome-Wide Open Chromatin Methylome Profiles in Colorectal Cancer

Ishak, Muhiddin; Baharudin, Rashidah; Rose, Isa Mohamed; Sagap, Ismail; Mazlan, Luqman; Azman, Zairul Azwan Mohd; Abu, Nadiah; Jamal, Rahman; Lee, Learn‐Han; Mutalib, Nurul Syakima Ab

doi:10.3390/biom10050719

Cited by 15 publications

(8 citation statements)

References 47 publications

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“…A few studies have shown the dysregulation of DNA methylation in colon cancer including EYA4 , which was hypermethylated and treatment with demethylating agents caused induction of its expression [ 46 ]. In agreement with Kim et al [ 31 ] and Moon et al [ 47 ], we have restored the expression of EYA4 after treating the Caco-2 and LoVo colon cancer cells with 1 μ M 5-Aza-CdR for 72 hours, this implies the possible mechanism of involvement of DNA methylation in hampering the expression of EYA4 [ 31 ], which could accelerate colon cancer formation [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Cigarette Smoke Regulates the Expression of EYA4 via Alternation of DNA Methylation Status

Almutairi

Alrefaei

et al. 2022

BioMed Research International

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Cigarette SMOKE (CS) considerably contributes to causing some diseases such as cancer, and it has a role in the alternation of gene expression through several mechanisms including epigenetics modification, particularly DNA methylation. EYA4 is one of the genes, that whose expression has been dysregulated in lung, colon, bladder, and breast cancer, leading to tumor progression. The alternation of DNA methylation levels has been implicated in regulating the expression of the EYA4 gene. Thus, in this study, we have shown the effect of CS on the DNA methylation level of the EYA4 promoter region as well as the methylation level on EYA4 expression. To determine the level of DNA methylation on the promoter region of the EYA4 gene, we have employed the bisulfite conversion treatment followed by the Sanger Sequence for 100 DNA samples taken from Saudi people (50 smokers and 50 nonsmokers). We found that 26% of DNA extracted from smoker samples is methylated, while there was no methylation identified in nonsmoker samples. Also, using the demethylating agents such as AZA on LoVo and Caco-2 cancer cell lines causes induction of transcription level of EYA4, implying the possible mechanism of DNA methylation in the upregulation of EYA4. These findings suggest the possible mechanism of CS in controlling the expression of EYA4 via changing the status of DNA methylation.

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Section: Discussionmentioning

confidence: 99%

Cigarette Smoke Regulates the Expression of EYA4 via Alternation of DNA Methylation Status

Almutairi

Alrefaei

et al. 2022

BioMed Research International

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“…Thirty-four studies were found; of them, only those using Infinium Human Methylation 450K and EPIC BeadChips and providing adequate raw and clinical data were selected for further analysis. Four studies, namely GSE99788 [ 38 ], GSE149282 [ 39 ], GSE122126 [ 40 ] and GSE105798 [ 41 ], were recruited for our analysis. The description of study groups and correlations is presented in Table 1 .…”

Section: Methodsmentioning

confidence: 99%

Methylation Status of Corticotropin-Releasing Factor (CRF) Receptor Genes in Colorectal Cancer

Παναγοπούλου

Cheretaki

Karaglani

et al. 2021

JCM

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The corticotropin-releasing factor (CRF) system has been strongly associated with gastrointestinal pathophysiology, including colorectal cancer (CRC). We previously showed that altered expression of CRF receptors (CRFRs) in the colon critically affects CRC progression and aggressiveness through regulation of colonic inflammation. Here, we aimed to assess the potential of CRFR methylation levels as putative biomarkers in CRC. In silico methylation analysis of CRF receptor 1 (CRFR1) and CRF receptor 2 (CRFR2) was performed using methylome data derived by CRC and Crohn’s disease (CD) tissues and CRC-derived circulating cell-free DNAs (ccfDNAs). In total, 32 and 33 differentially methylated sites of CpGs (DMCs) emerged in CRFR1 and CRFR2, respectively, between healthy and diseased tissues. The methylation patterns were verified in patient-derived ccfDNA samples by qMSP and associated with clinicopathological characteristics. An automated machine learning (AutoML) technology was applied to ccfDNA samples for classification analysis. In silico analysis revealed increased methylation of both CRFRs in CRC tissue and ccfDNA-derived datasets. CRFR1 hypermethylation was also noticed in gene body DMCs of CD patients. CRFR1 hypermethylation was further validated in CRC adjuvant-derived ccfDNA samples, whereas CRFR1 hypomethylation, observed in metastasis-derived ccfDNAs, was correlated to disease aggressiveness and adverse prognostic characteristics. AutoML analysis based on CRFRs methylation status revealed a three-feature high-performing biosignature for CRC diagnosis with an estimated AUC of 0.929. Monitoring of CRFRs methylation-based signature in CRC tissues and ccfDNAs may be of high diagnostic and prognostic significance in CRC.

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“…Human 5-oxoprolinase, OPLAH, was shown to be hypermethylated in our study, which had a significant impact on the gene’s downregulation, suggesting a possible contribution to CRC through the dysregulation of gene expression. Numerous investigations have also revealed that OPLAH is frequently hypermethylated in CRC versus normal tissues [ 40 , 60 ]. Despite a paucity of information on OPLAH methylation in cancer, several patents have been filed for its applicability in cancer detection.…”

Section: Discussionmentioning

confidence: 99%

Epigenome-Wide DNA Methylation Profiling in Colorectal Cancer and Normal Adjacent Colon Using Infinium Human Methylation 450K

Baharudin

Ishak

Yusof³

et al. 2022

Diagnostics

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The aims were to profile the DNA methylation in colorectal cancer (CRC) and to explore cancer-specific methylation biomarkers. Fifty-four pairs of CRCs and the adjacent normal tissues were subjected to Infinium Human Methylation 450K assay and analysed using ChAMP R package. A total of 26,093 differentially methylated probes were identified, which represent 6156 genes; 650 probes were hypermethylated, and 25,443 were hypomethylated. Hypermethylated sites were common in CpG islands, while hypomethylated sites were in open sea. Most of the hypermethylated genes were associated with pathways in cancer, while the hypomethylated genes were involved in the PI3K-AKT signalling pathway. Among the identified differentially methylated probes, we found evidence of four potential probes in CRCs versus adjacent normal; HOXA2 cg06786372, OPLAH cg17301223, cg15638338, and TRIM31 cg02583465 that could serve as a new biomarker in CRC since these probes were aberrantly methylated in CRC as well as involved in the progression of CRC. Furthermore, we revealed the potential of promoter methylation ADHFE1 cg18065361 in differentiating the CRC from normal colonic tissue from the integrated analysis. In conclusion, aberrant DNA methylation is significantly involved in CRC pathogenesis and is associated with gene silencing. This study reports several potential important methylated genes in CRC and, therefore, merit further validation as novel candidate biomarker genes in CRC.

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Genome-Wide Open Chromatin Methylome Profiles in Colorectal Cancer

Cited by 15 publications

References 47 publications

Cigarette Smoke Regulates the Expression of EYA4 via Alternation of DNA Methylation Status

Cigarette Smoke Regulates the Expression of EYA4 via Alternation of DNA Methylation Status

Methylation Status of Corticotropin-Releasing Factor (CRF) Receptor Genes in Colorectal Cancer

Epigenome-Wide DNA Methylation Profiling in Colorectal Cancer and Normal Adjacent Colon Using Infinium Human Methylation 450K

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