CARM1 AS A POTENTIAL TARGET FOR INDUCING DIFFERENTIATION IN NEUROBLASTOMA

This thesis was directed to study neuroblastoma pathology and the project has been developed in collaboration with Associazione Italiana Per la Lotta al Neuroblastoma (Gaslini Hospital Genova, Italy). Neuroblastoma is a tumor showing a variable degree of cell undifferentiation, which is directly related with bad prognosis. This feature is most likely a consequence of a perturbation in the process of differentiation of neural crest stem cells during the development of the symphatoadrenal lineage of the nervous system. Therefore, molecular modulators that induce differentiation may be effective in the treatment of this malignancy. In this context, arginine methylation has been shown to play a pivotal role in cell development and differentiation, driving a number of cell lineages to acquire a finally correct phenotype. In particular, CARM1 (the coactivator-associated arginine methyltransferase 1) has been found to negatively regulate differentiation of PC12 pheochromocytoma cells by methylating the HuD RNA-binding protein, a known determinant of the neuronal phenotype. These data suggest that CARM1 inhibition could represent a possible therapeutic approach for neuroblastoma treatment. The work presented in this thesis aimed to investigate the role of CARM1 in the process of neuronal differentiation of the SK-N-BE(2) neuroblastoma cell line model, in order to clarify the effects of its methylation activity on neuroblastoma differentiation, and the possible involvement of the HuD RNA-binding protein in this process.