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

miR-483家族对igf-ii产生非胰岛细胞瘤低血糖的诊断潜力。

  • 影响因子:5.04
  • DOI:10.1530/EJE-20-0706
  • 作者列表:"Nagao M","Fukuda I","Asai A","Esguerra JLS","Hizuka N","Eliasson L","Sugihara H
  • 发表时间:2021-01-01
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: 在产生胰岛素样生长因子II (igf-ii) 的非胰岛细胞瘤低血糖 (NICTH) 中,产生高分子量形式的igf-ii (大igf-ii) 作为自发性低血糖的原因。在IGF2基因的内含子损伤中编码的MicroRNA (miRNA)-483家族被认为与igf-ii共表达。在这里,我们测试了血清miR-483-5p和-3p水平是否与NICTH中大igf-ii的存在相关。 设计: 测试来自怀疑具有igf-ii产生NICTH的患者 (n = 42) 的血清样品。使用定量PCR评估MiR-483-5p和-3p水平。使用ELISA分析igf-ii水平。通过蛋白质印迹鉴定大igf-ii的存在。 结果: 32例患者血清中检出大igf-ii。具有大igf-ii的血清 (n = 32) 中的MiR-483-5p (P = 0.0015) 和-3p (p = 0.027) 水平显著高于没有大igf-ii的血清 (n = 10),而血清igf-ii水平 (P = 0.055) 在各组之间没有显著差异。miR-483-5p的中位血清浓度比miR-483-3p高 ~ 10倍。虽然观察到两种mirna之间的强相关性 (r = 0.844,P <0.0001),但两者都与血清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高于igf-ii (0.694) 检测大igf-ii的存在。 结论: 血清miR-483-5p和-3p水平与大igf-ii存在的关联提示了这些mirna对产生NICTH的igf-ii的诊断潜力。

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