Lu Y, Fei X-Q, Yang S-F, Xu B-K, Li Y-Y
Department of Endocrinology, Taizhou People's Hospital, Nantong University, Taizhou, Jiangsu, China.
Eur Rev Med Pharmacol Sci. 2015 Feb;19(4):624-9.
Menin, encoded by the Men1 gene, is responsible for β-cell tumor formation in patients with multiple endocrine neoplasia type 1. Recently, Menin has been proven to negatively regulate β-cell proliferation in several mouse models, including hyperglycemia. However, it is unclear how glucose regulates Menin expression in β-cells.
In the present study, quantitative real-time reverse transcriptase-polymerase chain reaction analysis was performed to detect the expression levels of MicroRNAs in Min-6 cells treated with high glucose, in which we found that miR-17 was significantly up-regulated.
Further studies using bioinformatic prediction, luciferase and protein expression analysis suggested that miR-17 could inhibit protein levels of Menin through targeting its 3'-untranslated region.
Our results indicate that miR-17 might serve as an important intracellular target of glucose to mediate the mitogenic effect that glucose exerts in pancreatic β-cells.
由Men1基因编码的Menin蛋白，在1型多发性内分泌肿瘤患者中负责β细胞肿瘤的形成。最近，在包括高血糖在内的几种小鼠模型中，Menin已被证明对β细胞增殖具有负调控作用。然而，尚不清楚葡萄糖如何调节β细胞中Menin的表达。
在本研究中，通过定量实时逆转录聚合酶链反应分析，检测高糖处理的Min-6细胞中MicroRNAs的表达水平，我们发现miR-17显著上调。
使用生物信息学预测、荧光素酶和蛋白质表达分析的进一步研究表明，miR-17可通过靶向Menin的3'-非翻译区来抑制其蛋白水平。
我们的结果表明，miR-17可能作为葡萄糖的重要细胞内靶点，介导葡萄糖在胰腺β细胞中发挥的促有丝分裂作用。
