Identification of non-coding RNA – based molecular networks in Group 3 Medulloblastoma

Cancer is a complex genetic disease involving structural and expression abnormalities of both coding and non-coding genes. These latters include long, small and even circular transcripts, which are crucial players in the multi-layered gene expression regulation playing key roles in every cellular process. Medulloblastoma (MB) is the most common malignant childhood brain tumour; the current therapeutic approaches cause long-term side effects, which could be avoided by using molecularly targeted therapies. Recently, insights gained from transcriptomic and genomic analyses revealed the existence of four MB molecular subgroups (WNT, SHH, Group 3 and Group 4), each considered as a distinct disease and marked by specific driver genes. While WNT and SHH MB subgroups have been thoroughly investigated, great efforts are required to better characterize Group 3 and Group 4 MBs, which account for 60% of all prognoses and present the greatest clinical challenges. In this regard, I previously contributed to discover the role of the long non-coding RNA linc-NeD125 as a competing endogenous RNA that regulates the expression of specific Group 4 MB driver genes. I am still focusing on the molecular pathways deregulated in MB to identify non-coding RNA – based molecular networks underlying the enigmatic Group 3 MB, which shows the worst outcome and the highest metastasis rate. This subgroup is characterized by a MYC signature, due to both gene copy number increase and aberrant expression. Transcriptomic analyses on a Group 3 – derived cell line (D283-Med cells) interfered for MYC expression are allowing me to produce an atlas of RNA species (mRNAs, long ncRNAs, small ncRNAs, circRNAs) regulated by MYC. The final goal is to build up novel non-coding RNA – based molecular circuitries as well as to identify novel biomarkers and potential therapeutic targets of Group 3 MB.