Gene expression and methylation profiles show the involvement of POMC in primary hyperparathyroidsm

Abstract

Primary hyperparathyroidism (PHPT) is mainly caused by parathyroid adenoma, which produces excess parathyroid hormones. Its pathogenic mechanisms have not yet been fully understood. To investigate the mechanism in the pathogenesis of PHPT, the transcriptome and genome-wide DNA methylation profiles of parathyroid adenoma were analyzed. The candidate genes that may be involved in the PHPT were verified via qRT-PCR, immunohistochemistry, western blot, and methylation-specific PCR. A total of 1650 differentially expressed genes and 2373 differentially methylated regions were identified. After the integration of its transcriptome and DNA methylation data, IL6, SYP, GNA01, and pro-opiomelanocortin (POMC) were the candidate genes that demonstrated a similar pattern between their mRNA expression and DNA methylation status. Of the 4 candidate genes, POMC, a pro-peptide which is processed to a range of bioactive peptide products like ACTH, was further confirmed to be expressed at low levels at both the mRNA and protein levels, which may be due to POMC promoter hypermethylation. Hypermethylation of the POMC promoter may contribute to its low expression, which may be involved in the pathogenesis of PHPT.

High lymphocyte signature genes expression in parathyroid endocrine cells and its downregulation linked to tumorigenesis

“…Consistent with our findings, a previous study has reported the down-regulation of POMC in parathyroid adenomas samples. 39 Our single-cell study provides further evidence that the downregulation of POMC expression is located in PTH + cells. Our data also highlighted CD4, CD226, ART5 and GPR32, which have not been reported, as suggestive biomarkers that were potentially involved in adenoma initiation and progression.…”

DNA Methylation of POMC and NR3C1-1F and Its Implication in Major Depressive Disorder and Electroconvulsive Therapy

“…Interpretation of our study is further hindered by (a) the partial heterogeneity of the groups studied (ECT patients were older than control subjects), (b) conflicting results regarding NR3C1m in the literature, (c) the lack of data complementary to our DNAm analysis (neither mRNA nor protein expression was evaluated), (d) the very small differences in methylation levels, (e) the fact that DNAm between brain and periphery may greatly differ, and (f) the weak association between DNAm and gene expression in general. Regarding the latter (f), however, recent studies found that the DNAm of NR3C1-1F and POMC were inversely correlated with NR3C1 and POMC (and thus ACTH), respectively [44][45][46].…”

Advances in the molecular genetics of parathyroid tumors

“…Hypermethylation of CpG islands and low expression of the POMC gene were found in parathyroid adenoma tissues compared with normal parathyroid tissues, suggesting that hypermethylation of the POMC gene may be associated with the development of parathyroid adenomas. [ 13 ] This finding provides a new approach for investigating the pathogenesis of parathyroid adenomas by examining other endocrine axes.…”