Arginine-rich, cell penetrating peptide-anti-microRNA complexes decrease glioblastoma migration potential

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 R-8 peptide condensed both siRNA and anti-miRNA. Greater than 50% of cells had anti-miRNA/R-8 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 R-8 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/R-8 complexes, which has laid the groundwork for further exploring octaarginine as intracellular anti-miRNAs carrier. (C) 2014 Elsevier Inc. All rights reserved.