Université catholique de Louvain, de Duve Institute, 75 Avenue Hippocrate 7529, B-1200 Brussels, Belgium.
Biochem Biophys Res Commun. 2010 Jan 1;391(1):293-8. doi: 10.1016/j.bbrc.2009.11.052. Epub 2009 Nov 12.
MicroRNAs are small, non-coding RNAs that posttranscriptionally regulate gene expression mainly by binding to the 3'UTR of their target mRNAs. Recent data revealed that microRNAs have an important role in pancreas and liver development and physiology. Using cloning and microarray profiling approaches, we show that a unique repertoire of microRNAs is expressed at the onset of liver and pancreas organogenesis, and in pancreas and liver at key stages of cell fate determination. Among the microRNAs that are expressed at these stages, miR-495 and miR-218 were predicted to, respectively, target the Onecut (OC) transcription factors Hepatocyte Nuclear Factor-6 (HNF-6/OC-1) and OC-2, two important regulators of liver and pancreas development. MiR-495 and miR-218 are dynamically expressed in developing liver and pancreas, and by transient transfection, we show that they target HNF-6 and OC-2 3'UTRs. Moreover, when overexpressed in cultured cells, miR-495 and miR-218 decrease the endogenous levels of HNF-6 and OC-2 mRNA. These results indicate that the expression of regulators of liver and pancreas development is modulated by microRNAs. They also suggest a developmental role for miR-495 and miR-218.
微小 RNA 是小的非编码 RNA，主要通过与靶 mRNA 的 3'UTR 结合来转录后调节基因表达。最近的数据表明，微小 RNA 在胰腺和肝脏的发育和生理中具有重要作用。使用克隆和微阵列分析方法，我们表明在肝脏和胰腺器官发生的起始以及在胰腺和肝脏中细胞命运决定的关键阶段，表达了一组独特的微小 RNA。在这些阶段表达的微小 RNA 中，miR-495 和 miR-218 分别被预测靶向转录因子 Onecut (OC) Hepatocyte Nuclear Factor-6 (HNF-6/OC-1) 和 OC-2，这两个是肝脏和胰腺发育的重要调节因子。miR-495 和 miR-218 在发育中的肝脏和胰腺中动态表达，通过瞬时转染，我们表明它们靶向 HNF-6 和 OC-2 3'UTR。此外，当在培养细胞中过表达时，miR-495 和 miR-218 降低内源性 HNF-6 和 OC-2 mRNA 的水平。这些结果表明，肝脏和胰腺发育调节剂的表达受微小 RNA 调节。它们还表明 miR-495 和 miR-218 具有发育作用。
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