MiR-495 and miR-218 regulate the expression of the Onecut transcription factors HNF-6 and OC-2

MiR-495 and miR-218 regulate the expression of the Onecut transcription factors HNF-6 and OC-2
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DOI:
10.1016/j.bbrc.2009.11.052
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发表时间:
2010-01-01
影响因子:
3.1
通讯作者:
Jacquemin, Patrick
Jacquemin, Patrick
中科院分区:
生物学4区
文献类型:
--
作者:
Simion, Alexandru;Laudadio, Ilaria;Jacquemin, Patrick

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MicroRNA 是小型非编码 RNA,主要通过与其靶 mRNA 的 3'UTR 结合来转录后调节基因表达。最近的数据表明,microRNA 在胰腺和肝脏的发育和生理学中发挥着重要作用。使用克隆和微阵列分析方法,我们展示了在肝脏和胰腺器官发生开始时表达的独特的 microRNA 库。在细胞表面确定关键阶段的胰腺和肝脏中,在这些阶段表达的 microRNA 中,miR-495 和 miR-218 预计分别靶向 Onecut (OC) 转录因子肝细胞核因子 - 6 (HNF-6/OC-1) 和 OC-2。肝脏和胰腺发育的两个重要调节因子 miR-495 和 miR-218 通过瞬时转染在发育中的肝脏和胰腺中动态表达。我们发现它们靶向 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 会降低 HNF-6 和 OC-2 mRNA 的内源水平。这些结果表明肝脏和胰腺发育调节因子的表达受到 microRNA 的调节。它们还表明 miR-495 和 miR-218 的发育作用 (C) 2009 Elsevier Inc 保留所有权利
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 ail important role in pancreas and liver development and physiology. Using cloning and microarray profiling approaches, we show chat a unique repertoire of microRNAs is expressed at the onset of liver and pancreas organogenesis. and in pancieas and liver at key stages of cell face 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 (C) 2009 Elsevier Inc All rights reserved