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