ArticleThe Journal of clinical endocrinology and metabolism2020
Reduced Calcium Sensing Receptor (CaSR) Expression Is Epigenetically Deregulated in Parathyroid Adenomas.
Article in The Journal of clinical endocrinology and metabolism, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 46 citations in OpenAlex.
- Inhibition of Calcium-Sensing Receptor Suppresses Malignant Behaviours of Human Hepatocellular Carcinoma.Journal of cellular and molecular medicine · 2026Article
- Normo-hormonal primary hyperparathyroidism presenting with recurrent acute pancreatitis.JCEM case reports · 2026Article
- Immunohistological parathormone production changes and angiogenesis in normal and adenomatous human parathyroid glands.Histology and histopathology · 2026Article
- Immunohistochemical Expression of CaSR, VDR, and AMA in Parathyroid Tumors in Relation to Hypercalcemia Severity in Primary Hyperparathyroidism.Current issues in molecular biology · 2026Article
- Low forearm bone density as a clue to suspect primary hyperparathyroidism in postmenopausal women with osteoporosis: a retrospective study.Archives of osteoporosis · 2026Article
- Metal Ions Within the Neuro-Immune-Tumor Axis.Journal of immunology research · 2026Review
- Tubular functional capacity and maladaptive parathyroid hormone response in early-stage chronic kidney disease.Biomolecules & biomedicine · 2025Article
- Hypermethylation of the p16Acta histochemica et cytochemica · 2025Article
- Protein Signatures of Parathyroid Adenoma according to Tumor Volume and Functionality.Endocrinology and metabolism (Seoul, Korea) · 2024Article
- Epigenetic profiling reveals key genes and cis-regulatory networks specific to human parathyroids.Nature communications · 2024Article
- Genetics of hereditary forms of primary hyperparathyroidism.Hormones (Athens, Greece) · 2024Review
- Molecular Genetic Aspects of Sporadic Multiglandular Primary Hyperparathyroidism.Physiological research · 2023Review
- Article
- Molecular and Clinical Spectrum of Primary Hyperparathyroidism.Endocrine reviews · 2023Article
- [The role of calcium sensitive and vitamin D receptors in the pathogenesis of sporadic multiple parathyroid gland disease].Problemy endokrinologii · 2023Observational
- Genomic Profiling Reveals the Variant Landscape of Sporadic Parathyroid Adenomas in Chinese Population.The Journal of clinical endocrinology and metabolism · 2023Article
- Large parathyroid adenomas: Potential mechanisms to reconcile adenoma size and disease phenotype.Frontiers in endocrinology · 2023Article
- Revisiting Captain Charles Martell: witnessing the true face of primary hyperparathyroidism even in the twenty-first century.Archives of osteoporosis · 2022Article
- Patient-derived parathyroid organoids as a tracer and drug-screening application model.Stem cell reports · 2022Article
- Epidemiology, Pathophysiology, and Genetics of Primary Hyperparathyroidism.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022Review
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimReduced 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. EXPERIMENTAL
designForty 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.
resultsReal-time qPCR revealed reduced CaSR mRNA expression with a fold reduction of 0.12 (P < 0.0001) 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 < 0.002). 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 = 0.61; P < 0.003). Treatment with 5-aza-2'deoxycytidine restored the expression of CaSR in a parathyroid cell line.
conclusionOur data suggest that hypermethylation and increased H3K9me3 of the CaSR promoter 2 are involved in silencing CaSR expression in sporadic parathyroid adenoma.
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