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利用肽核酸探索 miR-9 参与神经发育。

Exploring miR-9 Involvement in Neural Development Using Peptide Nucleic Acids.

机构信息

Department of Environmental Science and Policy, Università degli Studi di Milano, 20133 Milano, Italy.

Department of Chemistry, Università degli Studi di Milano, 20133 Milano, Italy.

出版信息

Int J Mol Sci. 2020 Mar 15;21(6):2001. doi: 10.3390/ijms21062001.

Abstract

The microRNAs are small RNAs that regulate gene expression at the post-transcriptional level and can be involved in the onset of neurodegenerative diseases and cancer. They are emerging as possible targets for antisense-based therapy, even though the in vivo stability of miRNA analogues is still questioned. We tested the ability of peptide nucleic acids, a novel class of nucleic acid mimics, to downregulate miR-9 in vivo in an invertebrate model organism, the ascidian by microinjection of antisense molecules in the eggs. It is known that miR-9 is a well-conserved microRNA in bilaterians and we found that it is expressed in epidermal sensory neurons of the tail in the larva of . Larvae developed from injected eggs showed a reduced differentiation of tail neurons, confirming the possibility to use peptide nucleic acid PNA to downregulate miRNA in a whole organism. By identifying putative targets of miR-9, we discuss the role of this miRNA in the development of the peripheral nervous system of ascidians.

摘要

微小 RNA 是一种小的 RNA,在转录后水平调控基因表达,可参与神经退行性疾病和癌症的发生。它们正在成为反义治疗的可能靶点,尽管 miRNA 类似物的体内稳定性仍存在疑问。我们通过在无脊椎动物模式生物海鞘的卵子中显微注射反义分子,测试了肽核酸(一种新型核酸模拟物)在体内下调 miR-9 的能力。已知 miR-9 是后生动物中高度保守的 microRNA,我们发现它在幼虫尾部的表皮感觉神经元中表达。从注射卵中发育的幼虫显示出尾部神经元分化减少,证实了使用肽核酸 PNA 在整个生物体中下调 miRNA 的可能性。通过鉴定 miR-9 的假定靶标,我们讨论了该 miRNA 在海鞘周围神经系统发育中的作用。

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