miR-483 家族在 IGF-II 产生的非胰岛细胞瘤低血糖症中的诊断潜力。

Diagnostic potential of miR-483 family for IGF-II producing non-islet cell tumor hypoglycemia.

机构信息

Department of Endocrinology, Diabetes and Metabolism, Graduate School of Medicine, Nippon Medical School, Bunkyo-ku, Tokyo, Japan.

Islet Cell Exocytosis, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.

出版信息

Eur J Endocrinol. 2021 Jan;184(1):41-49. doi: 10.1530/EJE-20-0706.

DOI:10.1530/EJE-20-0706

PMID:33112286

Abstract

OBJECTIVE

In insulin-like growth factor II (IGF-II) producing non-islet cell tumor hypoglycemia (NICTH), high molecular weight forms of IGF-II (big IGF-II) are produced as a cause of spontaneous hypoglycemia. MicroRNA (miRNA)-483 family, encoded in an intron lesion of IGF2 gene, is suggested to be co-expressed with IGF-II. Here, we tested whether serum miR-483-5p and -3p levels are associated with the presence of big IGF-II in NICTH.

DESIGN

Serum samples from patients who were suspected to have IGF-II producing NICTH (n = 42) were tested. MiR-483-5p and -3p levels were evaluated using quantitative PCR. IGF-II level was analyzed using ELISA. The presence of big IGF-II was identified by Western blotting.

RESULTS

Big IGF-II was detected in the sera of 32 patients. MiR-483-5p (P = 0.0015) and -3p (P = 0.027) levels were significantly higher in sera with big IGF-II (n = 32) than in those without (n = 10), whereas serum IGF-II level (P = 0.055) was not significantly different between the groups. The median serum concentration of miR-483-5p was ~10 times higher than that of miR-483-3p. Although a strong correlation was observed between the two miRNAs (r = 0.844, P < 0.0001), but neither of which was correlated with serum IGF-II level. The areas under the receiver operating characteristic curves of miR-483-5p (0.853) and -3p (0.722) were higher than that of IGF-II (0.694) for detecting the presence of big IGF-II.

CONCLUSION

The associations of serum miR-483-5p and -3p levels with the presence of big IGF-II suggest the diagnostic potential of these miRNAs for IGF-II producing NICTH.

摘要

目的

胰岛素样生长因子 II（IGF-II）产生的非胰岛细胞瘤低血糖症（NICTH）中，会产生高分子量形式的 IGF-II（大 IGF-II），导致自发性低血糖。miRNA（miRNA）-483 家族位于 IGF2 基因内含子病变中，被认为与 IGF-II 共同表达。在这里，我们检测了血清 miR-483-5p 和 -3p 水平是否与 NICTH 中大 IGF-II 的存在有关。

设计

检测了疑似 IGF-II 产生的 NICTH 患者（n = 42）的血清样本。使用定量 PCR 评估 miR-483-5p 和 -3p 水平。使用 ELISA 分析 IGF-II 水平。通过 Western blot 鉴定大 IGF-II 的存在。

结果

在 32 名患者的血清中检测到大 IGF-II。在存在大 IGF-II 的血清中（n = 32），miR-483-5p（P = 0.0015）和 -3p（P = 0.027）水平明显高于不存在大 IGF-II 的血清（n = 10），而两组间血清 IGF-II 水平（P = 0.055）无显著差异。miR-483-5p 的血清浓度中位数约为 miR-483-3p 的 10 倍。尽管两种 miRNA 之间存在很强的相关性（r = 0.844，P < 0.0001），但它们都与血清 IGF-II 水平无关。miR-483-5p（0.853）和 -3p（0.722）的受试者工作特征曲线下面积均高于 IGF-II（0.694），用于检测大 IGF-II 的存在。