Department of Internal Medicine, CHA University School of Medicine, Chaum Life Center, Seoul, Korea.
Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.
Sci Rep. 2018 Aug 13;8(1):12016. doi: 10.1038/s41598-018-30484-9.
MicroRNAs (miRNAs) are dysregulated in many tumors; however, miRNA regulation in parathyroid tumors remains poorly understood. To identify differentially expressed miRNAs between sporadic and hereditary parathyroid tumors and to analyze their correlation with clinicopathological features, a microarray containing 887 miRNAs was performed; then, the differentially expressed miRNAs were validated by qRT-PCR using 25 sporadic and 12 hereditary parathyroid tumors and 24 normal parathyroid tissue samples. A receiver operating characteristic curve (ROC) analysis was applied to evaluate the utility of the miRNAs for distinguishing parathyroid tumor types. Compared to the miRNAs in the normal parathyroid tissues, 10 miRNAs were differentially expressed between the sporadic and hereditary parathyroid tumors. Seven of these miRNAs (let-7i, miR-365, miR-125a-3p, miR-125a-5p, miR-142-3p, miR-193b, and miR-199b-5p) were validated in the parathyroid tumor samples. Among these miRNAs, only miR-199b-5p was differentially expressed (P < 0.001); miR-199b-5p was significantly downregulated and negatively associated with PTH levels (γ = -0.579, P = 0.002) in the sporadic tumors but was upregulated in the hereditary tumors. This miRNA showed 67% sensitivity and 100% specificity for distinguishing sporadic and hereditary parathyroid tumors. These results reveal altered expression of a miRNA between sporadic and hereditary parathyroid tumors and the potential role of miR-199b-5p as a novel biomarker for distinguishing these two types of parathyroid tumors.
微小 RNA（miRNAs）在许多肿瘤中失调；然而，甲状旁腺肿瘤中的 miRNA 调节仍知之甚少。为了鉴定散发性和遗传性甲状旁腺肿瘤之间差异表达的 miRNAs，并分析它们与临床病理特征的相关性，进行了包含 887 个 miRNAs 的微阵列分析；然后，使用 25 个散发性和 12 个遗传性甲状旁腺肿瘤以及 24 个正常甲状旁腺组织样本通过 qRT-PCR 验证差异表达的 miRNAs。应用接受者操作特征曲线（ROC）分析评估 miRNA 区分甲状旁腺肿瘤类型的效用。与正常甲状旁腺组织中的 miRNAs 相比，10 个 miRNAs 在散发性和遗传性甲状旁腺肿瘤之间差异表达。这 10 个 miRNAs 中的 7 个（let-7i、miR-365、miR-125a-3p、miR-125a-5p、miR-142-3p、miR-193b 和 miR-199b-5p）在甲状旁腺肿瘤样本中得到验证。在这些 miRNAs 中，只有 miR-199b-5p 差异表达（P < 0.001）；miR-199b-5p 在散发性肿瘤中显著下调且与 PTH 水平呈负相关（γ=-0.579，P=0.002），而在遗传性肿瘤中上调。该 miRNA 对区分散发性和遗传性甲状旁腺肿瘤的敏感性为 67%，特异性为 100%。这些结果揭示了散发性和遗传性甲状旁腺肿瘤之间 miRNA 的表达改变，以及 miR-199b-5p 作为区分这两种类型甲状旁腺肿瘤的新型生物标志物的潜在作用。
