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

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.