{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:20:51Z","timestamp":1790785251585,"version":"4.1.0"},"reference-count":37,"publisher":"The Endocrine Society","issue":"9","license":[{"start":{"date-parts":[[2020,7,1]],"date-time":"2020-07-01T00:00:00Z","timestamp":1593561600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","award":["3\/1\/3-JRF2014\/HRD-57"],"award-info":[{"award-number":["3\/1\/3-JRF2014\/HRD-57"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Department of Science and Technology, New Delhi","award":["EMR\/2016\/005956"],"award-info":[{"award-number":["EMR\/2016\/005956"]}]},{"name":"Postgraduate Institute of Medical Education and Research","award":["71\/8-Edu-15\/2544"],"award-info":[{"award-number":["71\/8-Edu-15\/2544"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK43858"],"award-info":[{"award-number":["DK43858"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aim<\/jats:title>\n                  <jats:p>Reduced calcium sensing receptor (CaSR) expression has been implicated in parathyroid tumorigenesis, but the underlying mechanism remains elusive. Accordingly, we aimed to explore the epigenetic changes (DNA methylation and histone modifications) involved in CaSR regulation in sporadic parathyroid adenomas and correlate epigenetic state with disease indices.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Experimental Design<\/jats:title>\n                  <jats:p>Forty sporadic parathyroid adenomas and 10 control parathyroid tissues were studied. Real-time quantitative PCR (qPCR) for mRNA and immunohistochemistry for protein expression of CaSR were performed. The methylation status of the CaSR promoter 2 was determined by bisulphite sequencing analysis of sodium bisulphite-converted DNA. To determine the role of histone modifications in the CaSR regulation, chromatin immunoprecipitation-qPCR assay was performed.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Real-time qPCR revealed reduced CaSR mRNA expression with a fold reduction of 0.12 (P\u2005&amp;lt;\u20050.0001) in parathyroid adenomas. Immunohistochemistry revealed reduced protein expression of CaSR in 90% (36\/40) of adenomas. The promoter 2 region of CaSR displayed significant hypermethylation in 45% (18\/40) of the adenomas compared with the controls (6.7%; 1 of 10) (P\u2005&amp;lt;\u20050.002). Bisulphite sequencing analysis revealed maximum methylated CpG at glial cell missing 2 binding site on the CaSR promoter 2 compared to other CpG sites. The methylation status of CaSR correlated directly with plasma intact parathyroid hormone levels in patients with parathyroid adenoma. With chromatin immunoprecipitation-qPCR analysis, H3K9me3 levels showed increased enrichment by 10-fold in adenomas and correlated with CaSR-mRNA expression (r\u2005=\u20050.61; P\u2005&amp;lt;\u20050.003). Treatment with 5-aza-2\u2032deoxycytidine restored the expression of CaSR in a parathyroid cell line.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Our data suggest that hypermethylation and increased H3K9me3 of the CaSR promoter 2 are involved in silencing CaSR expression in sporadic parathyroid adenoma.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgaa419","type":"journal-article","created":{"date-parts":[[2020,7,1]],"date-time":"2020-07-01T18:04:37Z","timestamp":1593626677000},"page":"3015-3024","source":"Crossref","is-referenced-by-count":48,"title":["Reduced Calcium Sensing Receptor (CaSR) Expression Is Epigenetically Deregulated in Parathyroid Adenomas"],"prefix":"10.1210","volume":"105","author":[{"given":"Priyanka","family":"Singh","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Postgraduate Institute of Medical Education and Research 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Nahar","family":"Saikia","sequence":"additional","affiliation":[{"name":"Department of Histopathology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naresh","family":"Sachdeva","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jyotdeep","family":"Kaur","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Luisa","family":"Brandi","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Biomedical Sciences, University of Florence, 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