Aberrant histone methylation profile in patients with sporadic primary hyperparathyroidism
Recommended Citation
Kumari P, Bhadada SK, Arya AK, Kaur J, Sachdeva N, Saikia UN, Dahiya D, Kumar A, Kharbanda C, and Rao SD. Aberrant histone methylation profile in patients with sporadic primary hyperparathyroidism. J Clin Endocrinol Metab 2025.
Document Type
Article
Publication Date
12-15-2025
Publication Title
The Journal of clinical endocrinology and metabolism
Keywords
Histone H3; Primary hyperparathyroidism; histone methylation; trimethylation of lysine (K) 27 on histone-3; trimethylation of lysine (K) 36 on histone-3; trimethylation of lysine (K) 4 on histone-3
Abstract
INTRODUCTION: Primary hyperparathyroidism (PHPT) is a systemic endocrine disorder characterized by elevated parathyroid hormone (PTH) levels and hypercalcemia. Gene-specific epigenetic modifications like histone methylation play a pivotal role in PHPT by altering expression of parathyroid-specific genes. However, global histone modifications in parathyroid tumors and their implications for tumor behavior remain underexplored.
EXPERIMENTAL DESIGN: We performed comparative histone modification profiling in blood and tissue samples from sporadic parathyroid adenomas (PA; n=30), atypical parathyroid tumors (APT; n=05), and parathyroid carcinomas (PC; n=05) along with controls using histone H3 multiplex immunoassay. Significantly dysregulated modifications were validated by western blotting (WB) and expression data was correlated with clinicopathological features. We performed pathway enrichment analysis to elucidate molecular pathways potentially linked to histone H3 modifications in parathyroid tumorigenesis.
RESULTS: We observed dynamic alterations in histone H3 modifications of lysine (K) residues across parathyroid tumor phenotypes in blood and tissue samples. A reduction in H3K4, H3K36 trimethylation (< 60%) and increase in H3K27 trimethylation and H3K9 monomethylation (>130%) than controls was observed. WB confirmed lower H3K4me3 (0.5±0.4 vs 4.4±0.7, p=0.02; 0.4±0.2 vs 4.4±0.7, p=0.004) and H3K36me3 (0.4±0.2 vs 1.0±0.3, p=0.03; 0.2±0.1 vs 1.0±0.3, p=0.02) in APT and PC than controls, and higher H3K27me3 expression in PA (2.9±1.2 vs 1.1±0.21, p=0.04), APT (4.2±2.9 vs 1.1±0.21, p=0.007), and PC (6.9±3.1 vs 1.1±0.21, p=0.0002) relative to controls. Pathway enrichment analysis identified molecular pathways, including calcium signaling, Wnt, and Hippo signaling, associated with histone H3 modifications.
CONCLUSION: Increased expression of repressive H3K27me3 in blood and tissue samples, while decreased H3K4me3 and H3K36me3, suggest a shift towards transcriptional repression. Identifying their functional mechanisms may facilitate discovery of novel insights for therapeutic targeting in parathyroid tumors.
PubMed ID
41396875
ePublication
ePub ahead of print
