microRNA interaction with MAPK and AKT pathways in paediatric brain tumours – preliminary results and review of the literature

Abstract

Nowadays molecular investigations have a significant impact on the understanding of primary brain tumour biology,as well as on their classification and progress in the treatment modalities. Among novel type of biomarkers with potential therapeutic value, microRNAs (miRNAs) are considered in some cases. miRNAs are small molecules regu­lating gene expression, including genes encoding key proteins involved in signalling pathways responsible for growth and cell survival during tumour formation. Incorrectly hyperactivated pathways implicated in brain tumour development are inter alia the PI3K/AKT/mTOR and RAS/MAPK/ERK cascades associated with worse prognosis and decreased patient survival. This work presents relationships between changes in the expression of individual miRNAs and the genes involved in the regulation of PI3K/AKT/mTOR and RAS/MAPK/ERK signalling pathways in primary brain tumours. Herein we present the preliminary results of miR-17-5p and miR-20a (key representatives of the miR-17-92 oncogenic cluster) expression analysis and their connection with signalling pathway activation in two of the most frequent paediatric tumours: medulloblastoma and ependymoma. Our study was performed using the microarray and qPCR techniques and showed PI3K/AKT/mTOR and RAS/MAPK/ERK among the forefront of the list of pathways with the largest number of genes involved in their activation compared to the control. Predicted target analysis indicated the agents from miR-17-92 cluster within miRNAs regulating activity of PI3K/AKT/mTOR and RAS/MAPK/ERK deregulated genes. The expression level of key representatives of the oncogenic cluster, miR-17-5p, and miR-20a, increased with the WHO grade of the analysed cases; the highest levels were found in medulloblastomas.

Keywords

• brain tumour
• children
• ependymoma
• expression
• medulloblastoma
• mirna
• pi3k/akt/mtor
• ras/mapk/erk.