Verification of differentially expressed miRNA in parathyroid tumors of sporadic and hereditary forms

Abstract

Verification of differentially expressed miRNA in parathyroid tumors of sporadic and hereditary formsYOONJUNG CHUNGDepartment of Medical ScienceThe Graduate School, Yonsei University(Directed by Professor Yumie Rhee)BACKGROUDMicroRNAs (miRNAs) have been shown to be dysregulated in tumors; however, miRNA regulation of parathyroid tumorigenesis remains poorly understood. Here, we report expression of miRNA and correlation with clinical features in hereditary and sporadic parathyroid tumors to better understand the epigenetics changes.METHODSmiRNA arrays containing 887 human miRNAs were performed on total RNA extracted from parathyroid tumor samples from 6 patients with primary hyperparathyroidism (3 with sporadic tumors and 3 with hereditary tumors in patients with multiple endocrine neoplasia type 1, MEN 1) and 2 normal parathyroid tissues. Differentially expressed miRNA were validated by the TaqMan real-time quantitative PCR using RNU6 as endogenous control in 15 sporadic and 10 hereditary parathyroid tumors. Relative quantification was performed by Livak method with 20 normal parathyroid tissues as a calibrator.RESULTSUsing FDR < 0.05 from microarray data, we identified 10 differentially expressed miRNAs between normal parathyroid tissues vs. those from sporadic or hereditary tumors. Among them, putative tumor-suppressor miR-199b-5p was differentially expressed; significantly decreased and negatively correlated with PTH level in sporadic parathyroid tumors, meanwhile, upregulated and positively correlated with PTH level in hereditary parathyroid tumors. In agreement with these findings, clinical manifestations are much severe in sporadic parathyroid tumors than hereditary tumors regarding high calcium level correlated with a high PTH and larger tumor size. Even though there was not any significant direct relation between Menin target genes with miR-199b-5p, integration pathway analysis revealed a network between Menin itself and miR-199b-5p associated with cell cycle and proliferation. CONCLUSIONDown-, or up-regulation of miRNA-199b-5p seems to have a distinct role in the tumorigenesis leading to the phenotypic differences in sporadic and hereditary type of parathyroid tumors. This argues for the involvement of miRNAs with different manner in the pathogenesis of parathyroid tumors under different genetic background.