title: LNA-modified oligonucleotides mediate specific inhibition of microRNA function.
abstract: microRNAs are short, endogenous non-coding RNAs that act as post-transcriptional modulators of gene expression. Important functions for microRNAs have been found in the regulation of development, cellular proliferation and differentiation, while perturbed miRNA expression patterns have been observed in many human cancers. Here we present a method for specific inhibition of miRNA function through interaction with LNA-modified antisense oligonucleotides and report the specificity of this application. We show that LNA-modified oligonucleotides can inhibit exogenously introduced miRNAs with high specificity using a heterologous reporter assay, and furthermore demonstrate their ability to inhibit an endogenous miRNA in Drosophila melanogaster cells, leading to up-regulation of the cognate target protein. The method shows stoichiometric and reliable inhibition of the targeted miRNA and can thus be applied to studies of miRNA functions and validation of putative target genes.
authors.affiliation: Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Ulf Andersson
authors.initials: UA
authors.lastname: Ørom
authors.forename: Sakari
authors.initials: S
authors.lastname: Kauppinen
authors.forename: Anders H
authors.initials: AH
authors.lastname: Lund
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000737:chemistry / Q000494:pharmacology*; D016376:Oligonucleotides, Antisense / Q000737:chemistry / Q000494:pharmacology*; D013379:Substrate Specificity
chemical_list: D029721:Drosophila Proteins; C108880:HID protein, Drosophila; D035683:MicroRNAs; D009479:Neuropeptides; D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense; C477371:locked nucleic acid