Objectif Background and rationale: The Alu repeat elements are the most abundant short interspersed repeated elements (SINEs) in human genome. Recently, the accumulation of Alu RNA transcripts, following DICER1 deficit, has been shown to be responsible for a human disease, the dry form of age-related macular degeneration (AMD), Geographic Atrophy (GA). Interestingly, increased levels of Alu RNAs and reduced DICER1 expression have been observed in several cancers, although no correlation has yet been established.The main objective of the present proposal is to determine the potential role of Alu RNAs accumulation in tumor formation and progression.Specific aims: The project will focus on three aims: 1) the analysis of Alu RNA expression in cancer; 2) the study of Alu RNAs-mediated signal in cancer; and 3) the analysis of the inhibition of Alu RNAs accumulation in vivo.Methods: A panel of cancer cell lines and human tumors will be used for qRT-PCR, northern blot, western blot, immunohistochemical analyses and hypoxic studies, in order to determine the expression profile of Alu RNAs and its relation with DICER1 expression in cancer. To study Alu-mediated signaling, the potential involvement of inflammasome and ERK1/2 activation in human tumors and in the cancer cell lines, which express high Alu RNAs levels, will be assessed, carrying out western blot, qRT-PCR, ELISA assays and immunohistochemical analyses. The effect of Alu RNA accumulation on cell fate will be assessed, by performing proliferation, migration and tumorigenesis assays. Stable clones, in which Alu RNAs expression is inhibited, will be generated to study whether inhibition of Alu RNAs accumulation affects tumor growth and metastasis dissemination.Expected outcome: Overall, these findings will provide new insights into the importance of Alu RNA sequences and the non-canonical DICER1 signaling in cancer development and progression, and potentially yield additional, new therapeutic targets. Champ scientifique medical and health sciencesclinical medicineophthalmologymedical and health sciencesclinical medicineoncologynatural sciencesbiological sciencesgeneticsRNAnatural sciencesbiological sciencesgeneticsgenomes Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) FP7-PEOPLE-2013-CIG - Marie-Curie Action: "Career Integration Grants" Appel à propositions FP7-PEOPLE-2013-CIG Voir d’autres projets de cet appel Régime de financement MC-CIG - Support for training and career development of researcher (CIG) Coordinateur CONSIGLIO NAZIONALE DELLE RICERCHE Contribution de l’UE € 100 000,00 Adresse PIAZZALE ALDO MORO 7 00185 Roma Italie Voir sur la carte Région Centro (IT) Lazio Roma Type d’activité Research Organisations Contact administratif Di Giacomo Alfredo (Dr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée