ArticleExperimental & molecular medicine2018
Whole genome MBD-seq and RRBS analyses reveal that hypermethylation of gastrointestinal hormone receptors is associated with gastric carcinogenesis.
Article in Experimental & molecular medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18 citing papers in PubMed, 31 citations in OpenAlex.
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- Pharmacological Mechanism ofMedicina (Kaunas, Lithuania) · 2023Article
- Role of epigenetics and the transcription factor Sp1 in the expression of the D prostanoid receptor 1 in human cartilage.Frontiers in cell and developmental biology · 2023Article
- Aberrant Methylation of Somatostatin Receptor 2 Gene Is Initiated in Aged Gastric Mucosa Infected withCancers · 2022Article
- Evaluating the tumor immune profile based on a three-gene prognostic risk model in HER2 positive breast cancer.Scientific reports · 2022Article
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- Analysis of Gastric Cancer Transcriptome Allows the Identification of Histotype Specific Molecular Signatures With Prognostic Potential.Frontiers in oncology · 2021Article
- An Advanced Systems Pharmacology Strategy RevealsFrontiers in cell and developmental biology · 2021Article
- Genome-wide methylation sequencing identifies progression-related epigenetic drivers in myelodysplastic syndromes.Cell death & disease · 2020Article
- Predicting Carcinogenic Mechanisms of Non-Genotoxic Carcinogens via Combined Analysis of Global DNA Methylation and In Vitro Cell Transformation.International journal of molecular sciences · 2020Article
- UVB induces cutaneous squamous cell carcinoma progression by de novo ID4 methylation via methylation regulating enzymes.EBioMedicine · 2020Article
- ONECUT2 upregulation is associated with CpG hypomethylation at promoter-proximal DNA in gastric cancer and triggers ACSL5.International journal of cancer · 2020Article
- MCM3AP-AS1 KD Inhibits Proliferation, Invasion, and Migration of PCa Cells via DNMT1/DNMT3 (A/B) Methylation-Mediated Upregulation of NPY1R.Molecular therapy. Nucleic acids · 2020Article
- Premalignant lesions and gastric cancer: Current understanding.World journal of gastrointestinal oncology · 2019Review
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10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DNA methylation is a regulatory mechanism in epigenetics that is frequently altered during human carcinogenesis. To detect critical methylation events associated with gastric cancer (GC), we compared three DNA methylomes from gastric mucosa (GM), intestinal metaplasia (IM), and gastric tumor (GT) cells that were microscopically dissected from an intestinal-type early gastric cancer (EGC) using methylated DNA binding domain sequencing (MBD-seq) and reduced representation bisulfite sequencing (RRBS) analysis. In this study, we focused on differentially methylated promoters (DMPs) that could be directly associated with gene expression. We detected 2,761 and 677 DMPs between the GT and GM by MBD-seq and RRBS, respectively, and for a total of 3,035 DMPs. Then, 514 (17%) of all DMPs were detected in the IM genome, which is a precancer of GC, supporting that some DMPs might represent an early event in gastric carcinogenesis. A pathway analysis of all DMPs demonstrated that 59 G protein-coupled receptor (GPCR) genes linked to the hypermethylated DMPs were significantly enriched in a neuroactive ligand-receptor interaction pathway. Furthermore, among the 59 GPCRs, six GI hormone receptor genes (NPY1R, PPYR1, PTGDR, PTGER2, PTGER3, and SSTR2) that play an inhibitory role in the secretion of gastrin or gastric acid were selected and validated as potential biomarkers for the diagnosis or prognosis of GC patients in two cohorts. These data suggest that the loss of function of gastrointestinal (GI) hormone receptors by promoter methylation may lead to gastric carcinogenesis because gastrin and gastric acid have been known to play a role in cell differentiation and carcinogenesis in the GI tract.
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