MicroRNA-7 directly targets Reg1 in pancreatic cells
MicroRNA-7 directly targets Reg1 in pancreatic cells
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DOI：
10.1152/ajpcell.00013.2019
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发表时间：
2019-08-01
影响因子：
5.5
通讯作者：
Tzanakakis, Emmanuel S.
中科院分区：
文献类型：
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作者：
Downing, Shawna;Zhang, Fan;Tzanakakis, Emmanuel S.
再生胰岛衍生(REG)蛋白。它们最先在胰腺中被发现，在正常和疾病状态下与促进增殖、防止细胞凋亡和增强分化有关，但对它们的表达调控知之甚少。我们假设Reg的表达受到microRNAs的影响。生物信息学分析预测REG1是microRNA-7(miR-7)的靶标，它影响胰岛β细胞的功能。为此，我们研究了miR-7对胰腺腺泡和胰岛β细胞REG1表达的影响。免疫组织化学染色和Western blotting结果显示，腺泡细胞中REG1的表达水平高于胰岛细胞。观察到miR-7的相互表达模式。MiR-7过表达导致REG1mRNA的抑制和REG1蛋白的分泌减少。恰恰相反。MIR-7基因敲除导致REG1表达增加。通过荧光素酶活性测定证实miR-7靶向REG1。相反，miR-7并不直接抑制人类REG1REG1A和REG1B的同源基因，这表明在REG表达的调节方面存在物种差异。这是对任何REG成员的microRNA调节的第一次描述，该研究有助于填补我们对REG蛋白生物学知识的空白，特别是在疾病背景下。
Regenerating islet-derived (Reg) proteins. which were first discovered in the pancreas, are associated with increased proliferation, prevention of apoptosis, and enhanced differentiation in normal and disease states, but very little is known about the regulation of their expression. We hypothesized that Reg expression is influenced by microRNAs. Bioinformatic analysis predicted Reg1 to be a target of microRNA-7 (miR-7), which influences pancreatic beta-cell function. To this end, we investigated the effects of miR-7 on Reg1 expression in pancreatic acinar and islet beta-cells. High levels of Reg1 were noted by immunostaining and Western blotting in acinar cells in contrast to islet cells. A reciprocal expression pattern was observed for miR-7. Overexpression of miR-7 resulted in Reg1 mRNA suppression and reduction of secreted Reg1 protein. Conversely. miR-7 knockdown led to increases in Reg1. Targeting of Reg1 by miR-7 was confirmed via luciferase activity assays. In contrast, miR-7 did not directly repress the human ortholog of Reg1 REG1A as well as REG1B indicating species differences in the regulation of Reg expression. This is the first account of microRNA modulation of any Reg member warranting studies to fill gaps in our knowledge of Reg protein biology, particularly in disease contexts.