Objectif
"Increasing evidence indicates that non coding RNAs play a major role in the regulation of gene expression. A significant fraction of the non-coding transcriptome is represented by large intervening non coding RNA (lincRNAs), which seem to be involved with the epigenetic control of gene expression through binding with several members of the Polycomb Repressive Complexes (PRCs). Recently, dysregulation of lincRNAs has been associated to cancer. The HOTAIR lincRNA triggers the invasive program of breast epithelial cells by promoting epigenetic remodelling (Gupta et al., 2010). Although this report suggests an impact of lincRNAs in the transition to the metastatic phenotype, the role of lincRNAs in transformation remains largely unexplored. In this project I want to define the role of lincRNAs in the pathogenesis of cancer, using acute promyelocytic leukaemia (APL) as a model system. APL accounts for more than 10% of all Acute Myeloid Leukemias and is characterized by reciprocal translocations involving the retinoic acid α-receptor (RARα). APL blasts respond to all-trans retinoic acid (ATRA) treatment with differentiation, which involves epigenetic remodelling. The availability of new sequencing technologies coupled to tiling arrays and to the power of new computational biology programs, makes it now possible to study the whole non–coding RNA transcriptome. Determining the pattern of expression of lincRNAs during ATRA-induced APL differentiation, defining their functional significance, and deciphering the network of interactions between lincRNAs, the PML-RARα chimeric protein and the PRCs, will contribute to a better understanding of the nature of epigenetic deregulation in cancer and ultimately represent the basis to develop new anti-cancer strategies."
Champ scientifique
Appel à propositions
FP7-PEOPLE-2010-IOF
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Régime de financement
MC-IOF - International Outgoing Fellowships (IOF)Coordinateur
10124 Torino
Italie