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Comparison of Peptide- and Lipid-Based Delivery of miR-34a-5p Mimic into PPC-1 Cells
Stockholm University, Faculty of Science, Department of Neurochemistry. University of Tartu, Estonia.
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Number of Authors: 6
2017 (English)In: Nucleic Acid Therapeutics, ISSN 2159-3337, E-ISSN 2159-3345, Vol. 27, no 5, 295-302 p.Article in journal (Refereed) Published
Abstract [en]

The microRNA (miRNA) microRNA-34a (miR-34a) regulates a number of genes involved in cell cycle control and is therefore considered to have a high therapeutic potential. MiR-34a expression is often down-regulated in cancer cells and its restoration has been shown to exert a tumor-suppressive effect. However, effective and safe delivery of synthetic miRNA analogs into cancer cells remains a challenge. The aim of this study was to evaluate cell-penetrating peptide PepFect (PF) 14 as a carrier for delivery of miR-34a-5p into human primary prostate carcinoma-1 (PPC-1) cells. Using microarray expression analysis, we identified a total of 3,283 (1,744 upregulated and 1,539 downregulated) differentially expressed genes in PF14: miR-34a-5p-transfected cells. In comparison, miR-34a-5p delivery with the commercially available lipid-based reagent siPORT-NeoFX (siPORT) had less robust effects on differential expression and affected fewer genes significantly (90 upregulated and 91 downregulated genes). Functional annotation revealed significant enrichment for downregulated genes in processes and pathways associated with the cell cycle and proliferation regulation in PF14: miR-34a-5p-transfected cells. Five genes (ARHGAP1, AXL, CDC25A, FOSL1, and PDGFRA) were identified and validated as relevant quantitative real-time polymerase chain reaction-based markers of miR-34a-5p transfection efficiency. Our experiments revealed novel potential miR-34a-5p targets and demonstrate that PF14 is a reliable transfection reagent for miRNA mimics characterized by high efficiency and low toxicity relative to lipid-based reagents.

Place, publisher, year, edition, pages
2017. Vol. 27, no 5, 295-302 p.
Keyword [en]
miR-34a, cell-penetrating peptide, PepFect14
National Category
Biological Sciences
Identifiers
URN: urn:nbn:se:su:diva-147848DOI: 10.1089/nat.2017.0670ISI: 000411866400005PubMedID: 28657476OAI: oai:DiVA.org:su-147848DiVA: diva2:1153471
Available from: 2017-10-30 Created: 2017-10-30 Last updated: 2017-10-30Bibliographically approved

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