Dataset Information

Aberrant Epigenetic Alteration of PAX1 Expression Contributes to Parathyroid Tumorigenesis.

ABSTRACT:

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.

SUBMITTER: Singh P

PROVIDER: S-EPMC8764231 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Publications

Aberrant Epigenetic Alteration of PAX1 Expression Contributes to Parathyroid Tumorigenesis.

Singh Priyanka P Bhadada Sanjay Kumar SK Arya Ashutosh Kumar AK Saikia Uma Nahar UN Sachdeva Naresh N Dahiya Divya D Kaur Jyotdeep J Brandi Maria Luisa ML Rao Sudhaker Dhanwada SD

The Journal of clinical endocrinology and metabolism 20220101 2

<h4>Context</h4>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.<h4>Objective</h4>We aimed to study potential epigenetic-mediated mechanism of PAX1 gene in sporadic parathyroid adenomas.<h4>Methods</h4>In parathyroid adenomas tissues, we analyzed the DNA methylation via bisulfite-specific polymerase chain reaction (BSP) and histone modif ...[more]

PMID: 34453169

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Project description:Background:Pancreatic ductal adenocarcinoma (PDAC) remains one of the most fatal malignancies due to its high morbidity and mortality. DNA methylation exerts a vital part in the development of PDAC. However, a mechanistic role of mutual interactions between DNA methylation and mRNA as epigenetic regulators on transcriptomic alterations and its correlation with clinical outcomes such as survival have remained largely uncovered in cancer. Therefore, elucidation of aberrant epigenetic alteration in the development of PDAC is an urgent problem to be solved. In this work, we conduct an integrative epigenetic analysis of PDAC to identify aberrant DNA methylation-driven cancer genes during the occurrence of cancer. Methods:DNA methylation matrix and mRNA profile were obtained from the TCGA database. The integration of methylation and gene expression datasets was analyzed using an R package MethylMix. The genes with hypomethylation/hypermethylation were further validated in the Kaplan-Meier analysis. The correlation analysis of gene expression and aberrant DNA methylation was also conducted. We performed a pathway analysis on aberrant DNG methylation genes identified by MethylMix criteria using ConsensusPathDB. Results:188 patients with both methylation data and mRNA data were considered eligible. A mixture model was constructed, and differential methylation genes in normal and tumor groups using the Wilcoxon rank test was performed. With the inclusion criteria, 95 differential methylation genes were detected. Among these genes, 74 hypermethylation and 21 hypomethylation genes were found. The pathway analysis revealed an increase in hypermethylation of genes involved in ATP-sensitive potassium channels, Robo4, and VEGF signaling pathways crosstalk, and generic transcription pathway. Conclusion:Integrated analysis of the aberrant epigenetic alteration in pancreatic ductal adenocarcinoma indicated that differentially methylated genes could play a vital role in the occurrence of PDAC by bioinformatics analysis. The present work can help clinicians to elaborate on the function of differentially methylated expressed genes and pathways in PDAC. CDO1, GJD2, ID4, NOL4, PAX6, TRIM58, and ZNF382 might act as aberrantly DNA-methylated biomarkers for early screening and therapy of PDAC in the future.

Dataset Information

Aberrant Epigenetic Alteration of PAX1 Expression Contributes to Parathyroid Tumorigenesis.

Context

Objective

Methods

Results

Conclusion

Publications

Aberrant Epigenetic Alteration of PAX1 Expression Contributes to Parathyroid Tumorigenesis.

Similar Datasets

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