The present study investigated the effects of the combined treatment of two peptide nucleic acids (PNAs), directed against microRNAs involved in caspase-3 mRNA regulation (miR-155-5p and miR-221-3p) in the temozolomide (TMZ)-resistant T98G glioma cell line. These PNAs were conjugated with an octaarginine tail in order to obtain an efficient delivery to treated cells. The effects of singularly administered PNAs or a combined treatment with both PNAs were examined on apoptosis, with the aim to determine whether reversion of the drug-resistance phenotype was obtained. Specificity of the PNA-mediated effects was analyzed by reverse transcription-quantitative polymerase-chain reaction, which demonstrated that the effects of R8-PNA-a155 and R8-PNA-a221 anti-miR PNAs were specific. Furthermore, the results obtained confirmed that both PNAs induced apoptosis when used on the temozolomide-resistant T98G glioma cell line. Notably, co-administration of both anti-miR-155 and anti-miR-221 PNAs was associated with an increased proapoptotic activity. In addition, TMZ further increased the induction of apoptosis in T98G cells co-treated with anti-miR-155 and anti-miR-221 PNAs.

Targeting miR‑155‑5p and miR‑221‑3p by peptide nucleic acids induces caspase‑3 activation and apoptosis in temozolomide‑resistant T98G glioma cells

Gasparello J.;
2019

Abstract

The present study investigated the effects of the combined treatment of two peptide nucleic acids (PNAs), directed against microRNAs involved in caspase-3 mRNA regulation (miR-155-5p and miR-221-3p) in the temozolomide (TMZ)-resistant T98G glioma cell line. These PNAs were conjugated with an octaarginine tail in order to obtain an efficient delivery to treated cells. The effects of singularly administered PNAs or a combined treatment with both PNAs were examined on apoptosis, with the aim to determine whether reversion of the drug-resistance phenotype was obtained. Specificity of the PNA-mediated effects was analyzed by reverse transcription-quantitative polymerase-chain reaction, which demonstrated that the effects of R8-PNA-a155 and R8-PNA-a221 anti-miR PNAs were specific. Furthermore, the results obtained confirmed that both PNAs induced apoptosis when used on the temozolomide-resistant T98G glioma cell line. Notably, co-administration of both anti-miR-155 and anti-miR-221 PNAs was associated with an increased proapoptotic activity. In addition, TMZ further increased the induction of apoptosis in T98G cells co-treated with anti-miR-155 and anti-miR-221 PNAs.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11577/3478491
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