trichostatin-a and Parathyroid-Neoplasms

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.. We aimed to study potential epigenetic-mediated mechanism of PAX1 gene in sporadic parathyroid adenomas.. 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.. 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.. 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.

Topics: Acetylation; Adenoma; Adolescent; Adult; Aged; Animals; Carcinogenesis; Case-Control Studies; Cell Line, Tumor; Decitabine; DNA Methylation; Epigenesis, Genetic; Female; Gene Expression Regulation, Neoplastic; Healthy Volunteers; Histone Code; Humans; Hydroxamic Acids; Male; Middle Aged; Paired Box Transcription Factors; Parathyroid Glands; Parathyroid Neoplasms; Parathyroidectomy; Promoter Regions, Genetic; Rats; Young Adult