Title

Aberrant epigenetic alteration of PAX1 expression contributes to parathyroid tumorigenesis

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

Share

COinS