Tang Xiaoqing, Muniappan Latha, Tang Guiliang, Ozcan Sabire
Department of Molecular and Cellular Biochemistry, University of Kentucky, College of Medicine, Lexington, 40536, USA.
RNA. 2009 Feb;15(2):287-93. doi: 10.1261/rna.1211209. Epub 2008 Dec 18.
MicroRNAs (miRNAs) are small noncoding ribonucleotides that bind mRNAs and function mainly as translational repressors in mammals. MicroRNAs have been implicated to play a role in many diseases, including diabetes. Several reports indicate an important function for miRNAs in insulin production as well as insulin secretion. We have recently carried out a screen in the pancreatic beta-cell line MIN6 to identify miRNAs with altered abundance in response to changes in glucose concentrations. This screen resulted in identification of 61 glucose-regulated miRNAs from a total of 108 miRNAs detectable in MIN6 cells. Many of the identified miRNAs, including miR-124a, miR-107, and miR-30d were up-regulated in the presence of high glucose. Only a few of the miRNAs, including miR-296, miR-484, and miR-690 were significantly down-regulated by high glucose treatment. Interestingly, we found that overexpression of miR-30d, one of the miRNAs up-regulated by glucose, increased insulin gene expression, while inhibition of miR-30d abolished glucose-stimulated insulin gene transcription. Overexpression or inhibition of miR-30d did not have any effect on insulin secretion. These data suggest that the putative target genes of miR-30d may be negative regulators of insulin gene expression.
微小RNA（miRNA）是一类小的非编码核糖核苷酸，其可与信使核糖核酸（mRNA）结合，在哺乳动物中主要作为翻译抑制因子发挥作用。微小RNA已被证实参与多种疾病的发生发展，包括糖尿病。多项报告表明，微小RNA在胰岛素生成及胰岛素分泌过程中发挥着重要作用。我们最近在胰腺β细胞系MIN6中进行了一项筛选，以鉴定在葡萄糖浓度变化时丰度发生改变的微小RNA。该筛选从MIN6细胞中可检测到的总共108种微小RNA中鉴定出61种受葡萄糖调节的微小RNA。许多已鉴定出的微小RNA，包括miR-124a、miR-107和miR-30d，在高糖环境下表达上调。只有少数微小RNA，包括miR-296、miR-484和miR-690，在高糖处理后显著下调。有趣的是，我们发现葡萄糖上调的微小RNA之一miR-30d的过表达可增加胰岛素基因表达，而抑制miR-30d则可消除葡萄糖刺激的胰岛素基因转录。miR-30d的过表达或抑制对胰岛素分泌均无任何影响。这些数据表明，miR-30d的假定靶基因可能是胰岛素基因表达的负调节因子。
