期刊
INTERNATIONAL JOURNAL OF ONCOLOGY
卷 41, 期 6, 页码 2119-2127出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/ijo.2012.1632
关键词
microRNAs; peptide nucleic acids; delivery; miR-221; p27(kip1)
类别
资金
- MIUR [20093N774P]
- Telethon [GGP10214]
- CIB (Interuniversity Consortium for Biotechnologies)
- Associazione Veneta per la Lotta alla Talassemia (AVLT), Rovigo
The activity of a peptide nucleic acid (PNA) targeting cancer-associated microRNA-221 is described. PNAs against miR-221 were designed in order to bind very efficiently to the target RNA strand and to undergo efficient uptake in the cells. A polyarginine-PNA conjugate targeted against miR-221 (Rpep-PNA-a221) showed both very high affinity for RNA and efficient cellular uptake without the addition of transfection reagents. Unmodified PNA with the same sequence displayed RNA binding, but cellular uptake was very poor. Consistently, only Rpep-PNA-a221 strongly inhibited miR-221. Targeting miR-221 by PNA resulted in i) lowering of the hybridization levels of miR-221 measured by RT-qPCR, ii) upregulation of p27(Kip1) gene expression, measured by RT-qPCR and western blot analysis. The major conclusion of this study is that efficient delivery of anti-miR PNA through a suitable peptide carrier (Rpep-PNA-a221) leads to inhibition of miR-221 activity, altering the expression of miR-221-regulated functions in breast cancer cells.
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