title: Arginine-rich, cell penetrating peptide-anti-microRNA complexes decrease glioblastoma migration potential.
abstract: MicroRNAs (miRNAs) are a class of gene regulators originating from non-coding endogenous RNAs. Altered expression, both up- and down-regulation, of miRNAs plays important roles in many human diseases. Correcting miRNA dysregulation by either inhibiting or restoring miRNA function may provide therapeutic benefit. However, efficient, nontoxic miRNA delivery systems are in need. Cell penetrating peptides (CPPs) have been widely exploited for protein, DNA, and RNA delivery. Few have examined CPP transfection efficiency with single stranded anti-miRNA. The R8 peptide condensed both siRNA and anti-miRNA. Greater than 50% of cells had anti-miRNA/R8 complexes associated and in these cells 68% of anti-miRNA escapes the endosome/lysosome. Single-stranded antisense miR-21 inhibitor (anti-miR-21) administered using the R8 peptide elicited efficient downstream gene upregulation. Glioblastoma cell migration was inhibited by 25% compared to the negative control group. To our knowledge, this is the first demonstration of miRNA modulation with anti-miR-21/R8 complexes, which has laid the groundwork for further exploring octaarginine as intracellular anti-miRNAs carrier.
authors: Department of Biopharmaceutical Sciences, University of Illinois, Chicago, IL 60612-7231, USA.
authors: Yu
authors: Y
authors: Zhang
authors: Department of Biopharmaceutical Sciences, University of Illinois, Chicago, IL 60612-7231, USA.
authors: Melanie
authors: M
authors: Köllmer
authors: Department of Biopharmaceutical Sciences, University of Illinois, Chicago, IL 60612-7231, USA.
authors: Jason S
authors: JS
authors: Buhrman
authors: Department of Biopharmaceutical Sciences, University of Illinois, Chicago, IL 60612-7231, USA.
authors: Mary Y
authors: MY
authors: Tang
authors: Department of Biopharmaceutical Sciences, University of Illinois, Chicago, IL 60612-7231, USA; Department of Bioengineering, University of Illinois, Chicago, IL 60607-7052, USA; Department of Ophthalmology and Visual Sciences, University of Illinois, Chicago, IL 60612-4319, USA. Electronic address: rag@uic.edu.
authors: Richard A
authors: RA
authors: Gemeinhart
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D057846:Cell-Penetrating Peptides / Q000737:chemistry / Q000494:pharmacology*; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D016372:RNA, Antisense / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D012334:RNA, Neoplasm / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014162:Transfection / Q000379:methods
chemical_list: D057846:Cell-Penetrating Peptides; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D016372:RNA, Antisense; D012334:RNA, Neoplasm
keywords: Anti-miRNAs; Cell penetrating peptide; Glioblastoma; miRNA-21; miRNAs