Arginine-rich,cell penetrating peptide–anti-microRNA complexes decrease glioblastoma migration potential |
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| Institution: | 1. Department of Biopharmaceutical Sciences, University of Illinois, Chicago, IL 60612-7231, USA;2. Department of Bioengineering, University of Illinois, Chicago, IL 60607-7052, USA;3. Department of Ophthalmology and Visual Sciences, University of Illinois, Chicago, IL 60612-4319, USA;1. Department of Dermatology, Brigham and Women''s Hospital, Boston, Massachusetts;2. Harvard Medical School, Boston, Massachusetts;3. University of Massachusetts Medical School, Worcester, Massachusetts;1. Department of Oncological Surgery, Yinzhou People''s Hospital, Yinzhou Hospital Affiliated to Medical School of Ningbo University, 251 Baizhang East Road, Ningbo 315040, China;2. Department of Clinical Laboratory, Yinzhou People''s Hospital, Yinzhou Hospital Affiliated to Medical School of Ningbo University, 251 Baizhang East Road, Ningbo 315040, China;1. Laboratory of Experimental Surgery, Department of General and Thoracic Surgery, Justus-Liebig-University, Feulgen-Str. 10-12, D-35385 Giessen, Germany;2. Department of Anesthesiology, Intensive Care and Pain Medicine, Justus-Liebig-University of Giessen and Marburg, Campus Giessen, Rudolf-Bucheim-Straße 7, 35392 Giessen, Germany;1. Department of Microbiology, School of Medicine, University of Athens, 75 Mikras Asias, 11527 Athens, Greece;2. Department of Microbiology, NICU Aglaia Kyriakou Children''s Hospital, University of Athens, Athens, Greece |
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| 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. |
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| Keywords: | miRNAs miRNA-21 Glioblastoma Anti-miRNAs Cell penetrating peptide |
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