Aberrant Epigenetic Alteration of PAX1 Expression Contributes to Parathyroid Tumorigenesis.

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.