{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:20:29Z","timestamp":1784557229577,"version":"3.55.0"},"reference-count":32,"publisher":"Bioscientifica","issue":"8","content-domain":{"domain":["erc.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,8,1]]},"abstract":"<jats:p>\n                    DNA methylation and demethylation regulate the transcription of genes. DNA methylation-associated gene expression of adrenal steroidogenic enzymes may regulate cortisol production in cortisol-producing adenoma (CPA). We aimed to determine the DNA methylation levels of all genes encoding steroidogenic enzymes involved in CPA. Additionally, the aims were to clarify the DNA methylation-associated gene expression and evaluate the difference of CPA genotype from others using DNA methylation data. Twenty-five adrenal CPA and six nonfunctioning adrenocortical adenoma (NFA) samples were analyzed. RNA sequencing and DNA methylation array were performed. The methylation levels at 118 methylation sites of the genes were investigated, and their methylation and mRNA levels were subsequently integrated. Among all the steroidogenic enzyme genes studied,\n                    <jats:italic>CYP17A1<\/jats:italic>\n                    gene was mainly found to be hypomethylated in CPA compared to that in NFA, and the Benjamini-Hochberg procedure demonstrated that methylation levels at two sites in the\n                    <jats:italic>CYP17A1<\/jats:italic>\n                    gene body were statistically significant.\n                    <jats:italic>PRKACA<\/jats:italic>\n                    mutant CPAs predominantly exhibited hypomethylation of\n                    <jats:italic>CYP17A1<\/jats:italic>\n                    gene compared with the\n                    <jats:italic>GNAS<\/jats:italic>\n                    mutant CPAs. Inverse associations between\n                    <jats:italic>CYP17A1<\/jats:italic>\n                    methylation in three regions of the gene body and its mRNA levels were observed in the NFAs and CPAs. In applying clustering analysis using\n                    <jats:italic>CYP17A1<\/jats:italic>\n                    methylation and mRNA levels, CPAs with\n                    <jats:italic>PRKACA<\/jats:italic>\n                    mutation were differentiated from NFAs and CPAs with a\n                    <jats:italic>GNAS<\/jats:italic>\n                    mutation. We demonstrated that CPAs exhibited hypomethylation of the\n                    <jats:italic>CYP17A1<\/jats:italic>\n                    gene body in CPA, especially in the\n                    <jats:italic>PRKACA<\/jats:italic>\n                    mutant CPAs. Methylation of\n                    <jats:italic>CYP17A1<\/jats:italic>\n                    gene may influence its transcription levels.\n                  <\/jats:p>","DOI":"10.1530\/erc-22-0115","type":"journal-article","created":{"date-parts":[[2022,6,8]],"date-time":"2022-06-08T11:47:17Z","timestamp":1654688837000},"page":"495-502","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-8","source":"Crossref","is-referenced-by-count":1,"title":["Association of DNA methylation with steroidogenic enzymes in Cushing\u2019s adenoma"],"prefix":"10.1530","volume":"29","author":[{"given":"Takaya","family":"Kodama","sequence":"first","affiliation":[{"name":"Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9225-8193","authenticated-orcid":true,"given":"Kenji","family":"Oki","sequence":"additional","affiliation":[{"name":"Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Otagaki","sequence":"additional","affiliation":[{"name":"Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryuta","family":"Baba","sequence":"additional","affiliation":[{"name":"Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Okada","sequence":"additional","affiliation":[{"name":"Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyotaka","family":"Itcho","sequence":"additional","affiliation":[{"name":"Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Kobuke","sequence":"additional","affiliation":[{"name":"Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaku","family":"Nagano","sequence":"additional","affiliation":[{"name":"Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5400-1162","authenticated-orcid":true,"given":"Haruya","family":"Ohno","sequence":"additional","affiliation":[{"name":"Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7014-6812","authenticated-orcid":true,"given":"Nobuyuki","family":"Hinata","sequence":"additional","affiliation":[{"name":"Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Arihiro","sequence":"additional","affiliation":[{"name":"Department of Anatomical Pathology, Hiroshima University Hospital, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9882-2082","authenticated-orcid":true,"given":"Celso E","family":"Gomez-Sanchez","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, G.V. 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