The Journal of clinical endocrinology and metabolism · 2022
Aberrant Epigenetic Alteration of PAX1 Expression Contributes to Parathyroid Tumorigenesis.
СтатьяНаблюдательное исследованиеПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Singh Priyanka, Bhadada Sanjay Kumar, Arya Ashutosh Kumar, Saikia Uma Nahar, Sachdeva Naresh, Dahiya Divya, Kaur Jyotdeep, Brandi Maria Luisa, Rao Sudhaker Dhanwada
Аннотация
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.
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.
Предметные рубрики MeSH
AcetylationAdenomaAdolescentAdultAgedAnimalsCarcinogenesisCase-Control StudiesCell Line, TumorDNA MethylationDecitabineEpigenesis, GeneticFemaleGene Expression Regulation, NeoplasticHealthy VolunteersHistone CodeHumansHydroxamic AcidsMaleMiddle AgedPaired Box Transcription FactorsParathyroid GlandsParathyroid NeoplasmsParathyroidectomyPromoter Regions, GeneticRatsYoung Adult