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Epigenetic enzymes are promising targets for cancer therapy due to their involvement in cellular processes leading to oncogenesis. Accordingly, a number of epi-drugs are currently under investigation. Lysine-specific demethylase 1 (LSD1) removes mono- and di-methylated groups from lysines 4 or 9 on histone H3, via a flavin adenine dinucleotide (FAD)-dependent oxidative reaction. In brain tumours, LSD1 is over-expressed and it is correlated with aggressive disease, suggesting that its inhibition might be considered as therapeutically relevant. The work done during my PHD has been focused on the understanding the role of LSD1 uncovering its potential functions as new potential therapeutic agent for neuroblastoma (NB) and glioblastoma (GBM) tumours. We have investigated on its role in different Brain tumours demonstrating that LSD1 depletion is involved in three tumour-associated pathways: Epithelial-mesenchymal-Transition (EMT); Autophagy and Senescence and that different pathways are affected in different Brain tumours. In conclusion, we propose that pharmacological targeting of LSD1 by small molecules could modulate autophagy, senescence, migration capability and invasiveness of cancer cells through targeting proteins and thus impairing the ability of cancers to metastasize.

Studies of alterations in histone methylation in cancer have led to the identification of histone methyltransferases and demethylases as novel targets for therapy. Lysine-specific demethylase 1 (LSD1, also known as KDM1A), demethylates H3K4me1/2, or H3K9me1/2 in a context-dependent manner. In addition to the well-studied role of LSD1 in the epigenetic regulation of histone methylation changes, LSD1 regulates the methylation dynamic of several non-histone proteins and participates in the assembly of different long noncoding RNA (lncRNA_ complexes. LSD1 is highly expressed in various cancers, playing a pivotal role in different cancer-related processes. Here, we summarized recent findings on the role of LSD1 in the regulation of different biological processes in cancer cells through dynamic methylation of non-histone proteins and physical association with dedicated lncRNA.