ELAVL3: A NEW PROTEIN PROMOTING THE GROWTH OF PRONEURAL GLIOBLASTOMA ?

Résumé 0

ELAVL3 is an RNA-binding protein, specifically expressed in terminally differentiated neurons. It is necessary for neuron differentiation and maintenance as well as for neuronal plasticity and memory. Bioinformatic analysis, based on The Cancer Genome Atlas data, showed that ELAVL3 expression is increased in gliobastoma multiforme (GBM) of the proneural subtype. It also revealed strong correlation between ELAVL3 and proneural signature gene expression. Those results suggest that the protein might be implicated in GBM development. However, because the role of ELAVL3 in malignant cells has not yet been investigated, it is not clear whether the increased protein expression is necessary for malignant cell tumoregenicity or if it is simply a byproduct of the expression of proneural genes. This study aims to assess the importance of the increased expression of ELAVL3 in proneural GBM stem cells (GSCs) and to clarify the putative role of the protein in the development of this malignancy. First of all, the ELAVL3 expression was determined in GSCs grown both as spheroids and as differentiated adherent cells. Then, its expression was suppressed in GSCs. Those cells were then used to perform a proliferation assay and injected as xenografts into mice, in an attempt to better understand ELAVL3 function. The results of the in vitro experiments showed that the ELAVL3 expression is higher in proneural GSCs compared to stem cells of the other subtypes, which is in agreement with the results of the bioinformatic data analysis. Proliferation assays also showed that non-ELAVL3 expressing cells have a lower proliferation rate than ELAVL3 expressing cells. Unfortunately, those results could not be confirmed by the results of the xenograft injections, due to the lack of data yielded by in vivo experimentation. The results showed aincreased expression of ELAVL3 in proneural GBM stem cells that has never been described before. It also revealed involvement of the protein in cell proliferation, thus offering potential new perspectives regarding its function and its implication in tumorigenesis. Further studies will be needed to confirm these findings and to establish the exact function of ELAVL3 proneural glioblastoma.