High levels of apoptosis are induced in human glioma cell lines by co-administration of peptide nucleic acids targeting miR-221 and miR-222

Brognara,Eleonora; Fabbri,Enrica; Montagner,Giulia; Gasparello,Jessica; Manicardi,Alex; Corradini,Roberto; Bianchi,Nicoletta; Finotti,Alessia; Breveglieri,Giulia; Borgatti,Monica; Lampronti,Ilaria; Milani,Roberta; Dechecchi,Maria  Cristina; Cabrini,Giulio; Gambari,Roberto

doi:10.3892/ijo.2015.3308

High levels of apoptosis are induced in human glioma cell lines by co-administration of peptide nucleic acids targeting miR-221 and miR-222

Authors:
- Eleonora Brognara
- Enrica Fabbri
- Giulia Montagner
- Jessica Gasparello
- Alex Manicardi
- Roberto Corradini
- Nicoletta Bianchi
- Alessia Finotti
- Giulia Breveglieri
- Monica Borgatti
- Ilaria Lampronti
- Roberta Milani
- Maria Cristina Dechecchi
- Giulio Cabrini
- Roberto Gambari
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Affiliations: Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy, Department of Chemistry, University of Parma, Parma, Italy, Laboratory of Molecular Pathology, University-Hospital of Verona, Verona, Italy
Published online on: December 24, 2015 https://doi.org/10.3892/ijo.2015.3308
Pages: 1029-1038

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Abstract

The biological activity of a combined treatment of U251, U373 and T98G glioma cell lines with two anti-miR PNAs, directed against miR‑221 and miR‑222 and conjugated with an ocataarginine tail (R8-PNA-a221 and R8-PNA-a222) for efficient cellular delivery, was determined. Apoptosis was analyzed, and the effect of the combined treatment of glioma cells with either or both PNAs on the reversion of drug-resistance phenotype was assessed in the temozolomide-resistant T98G glioma cell line. Selectivity of PNA/miRNA interactions was studied by surface plasmon resonance (SPR)-based Biacore analysis. Specificity of the PNA effects at the cellular level was analyzed by RT-qPCR. These experiments support the concept that the effects of R8-PNA-a221 and R8-PNA-a222 are specific. The studies on apoptosis confirmed that the R8-PNA-a221 induces apoptosis and demonstrated the pro-apoptotic effects of R8-PNA-a222. Remarkably, increased pro-apoptotic effects were obtained with the co-administration of both anti-miR‑221 and anti-miR‑222 PNAs. In addition, co-administration of R8-PNA-a221 and R8-PNA-a222 induced apoptosis of TMZ-treated T98G cells at a level higher than that obtained following singular administration of R8-PNA-a221 or R8-PNA-a222.

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