Mir-34a mimics are potential therapeutic agents for p53-mutated and chemo-resistant brain tumour cells.

摘要: Chemotherapeutic drug resistance and relapse remains a major challenge for paediatric (medulloblastoma) adult (glioblastoma) brain tumour treatment. Medulloblastoma tumours cell lines with mutations in the p53 signalling pathway have been shown to be specifically insensitive DNA damaging agents. The aim of this study was investigate potential triggering death mutated medulloblastoma cells by direct activation pro-death downstream activation. Since non-coding microRNAs (miRNAs) ability fine tune expression variety target genes, orchestrating multiple effects, we hypothesised that miRNA could induce chemo-resistant cells. Treatment etoposide, increased miR-34a levels p53-dependent fashion level transcription correlated sensitivity etoposide. activity validated measuring one its well described target: NADH dependent sirtuin1 (SIRT1). Whilst drugs directly targeting SIRT1, were potent trigger at high concentrations only, introduction synthetic mimics able glioblastoma lines. Our results show need functional signaling can bypassed