Identification and functional analysis of RNA binding proteins associated with the development of glioblastoma multiform

Abstract

Glioblastoma multiforme (GBM) is one of the most aggressive tumor types, with a median survival time of 15 months. Poor survival is explained by the fact that current treatments are not able to prevent tumor recurrence. Understanding basic aspects of GBM biology, such as its origin, development and resistance is crucial to develop more effective therapies. RNA binding proteins (RBPs) are among the molecules involved in the genesis and development of the GBM. RBPs are critical post-transcriptional gene expression regulators which are implicated in several cellular processes, like mRNA and miRNA processing, stability, degradation, polyadenylation, translation and splice site selection. Changes in their expression levels cause severe alterations in the cellular proteome, which may lead to diseases states and tumorigenesis. Here, we aim to identify RPBs related to the development and resistance of GBM. First, we will select those RBPs by screening gene expression databanks; next, in collaboration with Dr. Penalva's group, we will determine the impact of identified up regulated RBPs in proliferation, invasion, apoptosis and stem cell survival. mRNA targets of the three RBPs showing the most prominent impact on cancer related functions will be determined by the iCLIP approach; their relevance to GBM development will be revealed via bioinformatics studies that will map target genes to biological processes and pathways. In conclusion, we expected that the investigation of central elements that control post-transcriptional regulation in tumor cells, like RBPs, could unveil unknown aspects of GBM development and lead to new possibilities of therapies. (AU)