Aberrant epigenetic alteration of PAX1 expression contributes to parathyroid tumorigenesis
Recommended Citation
Singh P, Bhadada SK, Arya AK, Saikia UN, Sachdeva N, Dahiya D, Kaur J, Brandi ML, and Rao SD. Aberrant epigenetic alteration of PAX1 expression contributes to parathyroid tumorigenesis. J Clin Endocrinol Metab 2021.
Document Type
Article
Publication Date
8-28-2021
Publication Title
The Journal of clinical endocrinology and metabolism
Abstract
STUDY DESIGN: Primary hyperparathyroidism (PHPT) results from the hypersecretion of parathyroid hormone from parathyroid tumors. Transcription factor i.e. Paired box1 (PAX1) is active in the parathyroid gland development. In the present study, we analyzed the role of DNA methylation via bisulphite specific polymerase chain reaction (BSP) and histone modifications via chromatin immunoprecipitation (ChIP) in regulating the differential expression of PAX1 in parathyroid adenomas tissues.
RESULTS: The results showed that mRNA and protein expression of PAX1 was significantly reduced in parathyroid adenomas. Bisulphite 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< 0.004) in parathyroid adenomas. Furthermore, upon treatment with pharmacologic inhibitor i.e. 5'aza-2 deoxycytidine (DAC) 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.
PubMed ID
34453169
ePublication
ePub ahead of print
