We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Aberrant Epigenetic Alteration of PAX1 Expression Contributes to Parathyroid Tumorigenesis.
- Authors
Singh, Priyanka; Bhadada, Sanjay Kumar; Arya, Ashutosh Kumar; Saikia, Uma Nahar; Sachdeva, Naresh; Dahiya, Divya; Kaur, Jyotdeep; Brandi, Maria Luisa; Rao, Sudhaker Dhanwada
- Abstract
Context: Primary hyperparathyroidism (PHPT) results from the hypersecretion of parathyroid hormone from parathyroid tumors. A transcription factor, namely Paired box1 (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.
- Subjects
HYPERPARATHYROIDISM; PARATHYROID gland cancer; TRANSCRIPTION factors
- Publication
Journal of Clinical Endocrinology & Metabolism, 2022, Vol 107, Issue 2, pe783
- ISSN
0021-972X
- Publication type
Article
- DOI
10.1210/clinem/dgab626