分析皮质醇分泌性肾上腺皮质肿瘤中外泌体相关 microRNAs 的循环变化。
Analysis of circulating extracellular vesicle-associated microRNAs in cortisol-producing adrenocortical tumors.
机构信息
2nd Department of Medicine, Semmelweis University, 1088, Budapest, Szentkiralyi str. 46., Hungary.
Endocrinology Unit, Department of Medicine, University of Padua, Via Ospedale, 105, 35128, Padova, Italy.
出版信息
Endocrine. 2018 Feb;59(2):280-287. doi: 10.1007/s12020-017-1506-z. Epub 2018 Jan 3.
PURPOSE
Circulating microRNAs (miRNA) have been described in patients with adrenocortical tumors, but the expression of miRNAs in non-functioning and cortisol-producing tumors has not been yet compared. Therefore, the objective of this study was to evaluate the expression of plasma extracellular vesicle (EV)-associated microRNAs in patients with non-functioning adrenocortical adenoma (NFA), cortisol-producing adrenocortical adenoma (CPA) and cortisol-producing adrenocortical carcinoma (CP-ACC).
METHODS
Preoperative plasma EV samples of 13 NFAs, 13 CPAs and 9 CP-ACCs were subjected to extracellular vesicle isolation. miRNAs were investigated by targeted quantitative real-time PCR normalized to cel-miR-39 as reference. Five miRNAs have been selected for this analysis based on the previous studies including hsa-miR-22-3p, hsa-miR-27a-3p, hsa-miR-210-3p, hsa-miR-320b and hsa-miR-375.
RESULTS
We have observed significant overrepresentation of three miRNAs in both CPA and CP-ACC relative to NFA: hsa-miR-22-3p (p < 0.01 and p < 0.0001, respectively), hsa-miR-27a-3p (p < 0.05 in both comparisons) and hsa-miR-320b (p < 0.05 and p < 0.0001, respectively). Hsa-miR-320b has been significantly overrepresented in CP-ACC relative to CPA (p < 0.01). Hsa-miR-210-3p turned out to be significantly overrepresented only in CP-ACC compared to NFA (p < 0.05). Significant correlation was revealed between circulating miRNA concentrations and urinary free cortisol values for hsa-miR-22-3p, hsa-miR-27a-3p and hsa-miR-320b (p < 0.0001 for all) and cortisol after low-dose dexamethasone test for hsa-miR-22-3p and hsa-miR-320b (p < 0.05). Hsa-miR-27a-3p has been significantly stimulated by low-dose dexamethasone test (p < 0.05).
CONCLUSIONS
EV-associated miRNAs are differentially expressed in different non-functioning and cortisol-producing adrenocortical tumors.
目的
已有研究报道循环 microRNAs（miRNA）存在于肾上腺皮质肿瘤患者中，但非功能性和分泌皮质醇的肿瘤中 miRNA 的表达尚未进行比较。因此，本研究的目的是评估非功能性肾上腺皮质腺瘤（NFA）、分泌皮质醇的肾上腺皮质腺瘤（CPA）和分泌皮质醇的肾上腺皮质癌（CP-ACC）患者血浆细胞外囊泡（EV）相关 microRNAs 的表达。
方法
对 13 例 NFA、13 例 CPA 和 9 例 CP-ACC 的术前血浆 EV 样本进行 EV 分离。miRNA 采用靶向定量实时 PCR 检测，以 cel-miR-39 为内参进行归一化。根据之前的研究，选择了 5 个 miRNA 进行此分析，包括 hsa-miR-22-3p、hsa-miR-27a-3p、hsa-miR-210-3p、hsa-miR-320b 和 hsa-miR-375。
结果
与 NFA 相比，我们观察到 CPA 和 CP-ACC 中三种 miRNA 的过度表达：hsa-miR-22-3p（p<0.01 和 p<0.0001）、hsa-miR-27a-3p（p<0.05）和 hsa-miR-320b（p<0.05 和 p<0.0001）。hsa-miR-320b 在 CP-ACC 中相对于 CPA 过度表达（p<0.01）。与 NFA 相比，hsa-miR-210-3p 仅在 CP-ACC 中过度表达（p<0.05）。hsa-miR-22-3p、hsa-miR-27a-3p 和 hsa-miR-320b 的循环 miRNA 浓度与尿游离皮质醇值呈显著相关（所有 p<0.0001），hsa-miR-22-3p 和 hsa-miR-320b 的皮质醇与小剂量地塞米松试验呈显著相关（p<0.05）。hsa-miR-27a-3p 被小剂量地塞米松试验显著刺激（p<0.05）。
结论
不同的非功能性和分泌皮质醇的肾上腺皮质肿瘤中细胞外囊泡相关的 microRNAs 表达不同。
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