Circulating miRNA expression in glioblastoma patients & its effect on cell migration

Abstract

Glioblastoma Multiforme (GB) is the most common malignant human glioma and is currently incurable. Further understanding of the epigenetic mechanisms underpinning GB progression could facilitate earlier diagnosis and improve prognosis. MicroRNAs (miRNAs) are regions of RNA that reduce translation of proteins. Identifying dysregulated circulating miRNA(s) in sera could provide a potential biomarker for diagnosis, accessible through a blood test. GB and control sera supplied by Brain Tumour North West tissue bank was used to profile the circulating expression of miRNAs -20a, -34a, and -92a using quantitative PCR technology. The results were analysed according to age and sex, as well as overall comparison. MiRNA20a was reduced in GB samples as well as in 20–39 year-old (yo), 40–59 yo and male GB patients, but increased expression in GB patients aged 60 and over. MiRNA92a expression was reduced in 40-60yo GB patients however GB patients over the age of 60 showed an increased expression. MiRNA34a was reduced in GB patients overall, in both sexes and two out of three age groups (40–59, and 20–39 yo) when compared to age and sex matched control samples. The effect of miRNA 34a on cellular migration was analysed in human glioma and control human astrocyte cell lines by overexpression and knockdown. The cell lines were cultured in media containing pooled sera from GB patients, healthy individuals, standard fetal bovine serum and exosome depleted serum. Wound healing assays were performed to ascertain cell migration. Inhibition of miRNA 34a-5p significantly increased rate of migration in glioma cells cultured in human control sera. Acknowledgement should be made to Brain Tumour North West for providing the serum samples used in this study.