Journal
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
Volume 107, Issue 2, Pages E783-E792Publisher
ENDOCRINE SOC
DOI: 10.1210/clinem/dgab626
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Funding
- Department of Science and Technology-Science and Engineering Research Board, New Delhi, India [EMR/2016/005956]
- National Institute of Health (NIH) [DK43858]
- Henry Ford Health System
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This study investigated the epigenetic-mediated mechanism of the PAX1 gene in sporadic parathyroid adenomas. The results revealed that the expression of PAX1 was significantly reduced in parathyroid adenomas, which was associated with hypermethylation in the promoter region and lower levels of histone modification. Treatment with a pharmacologic inhibitor led to the re-expression of the PAX1 gene. These findings provide insights into the epigenetic deregulation of PAX1 in parathyroid adenomas and have potential clinical and therapeutic implications for patients with PHPT.
Context: Primary hyperparathyroidism (PHPT) results from the hypersecretion of parathyroid hormone from parathyroid tumors. A transcription factor, namely Paired box/ (PAX1), is active in parathyroid gland development. Objective: We aimed to study potential epigenetic-mediated mechanism of PAX1 gene in sporadic parathyroid adenomas. Methods: In parathyroid adenomas tissues, we analyzed the DNA methylation via bisulfite-specific polymerase chain reaction (BSP) and histone modifications via chromatin immunoprecipitation in regulating the differential expression of PAX1. Results: The results showed that mRNA and protein expression of PAX1 was significantly reduced in parathyroid adenomas. Bisulfite sequencing demonstrated hypermethylation in the promoter region of PAX1 (35%; 14/40) and lower levels of histone 3 lysine 9 acetylation (H3K9ac) were observed on the promoter region of PAX1 (6-fold; P < .004) in parathyroid adenomas. Furthermore, upon treatment with a pharmacologic inhibitor, namely 5'aza-2 deoxycytidine, in rat parathyroid continuous cells, we found re-expression of PAX1 gene. Conclusion: Our study not only reveals expression of PAX1 is epigenetically deregulated but also paves a way for clinical and therapeutic implications in patients with PHPT.
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