Functional and Mecahnistic Roles of Large Intergenic Non-coding RNAs in Cancer

Objectif

Mammalian cells express thousands of RNA molecules structurally similar to protein coding genes –they are large, spliced, poly-adenylated, transcribed by RNA Pol II, with conserved promoters and exonic structures –however lack coding capacity. Although thousands exist, only few of these large intergenic non-coding RNAs (lincRNAs) have been characterized. The few that have, show powerful biological roles as regulators of gene expression by diverse epigenetic and non-epigenetic mechanisms. Significantly, their expression patterns suggest that some lincRNAs are involved in cellular pathways critical in cancer, like the p53 pathway. I explored this association demonstrating that p53 induces the expression of many lincRNAs. One them, named lincRNA-p21, is directly induced by p53 to play a critical role in the p53 response, being required for the global repression of genes that interfere with p53 induction of apoptosis. My results, together with the emerging evidence in the field, suggest that lincRNAs may play key roles in numerous tumor-suppressor and oncogenic pathways, representing an unknown paradigm in cellular transformation. However, their mechanisms of function and biological roles remain largely unexplored.
The goal of this project is to decipher the functional and biological roles of lincRNAs in the context of oncogenic pathways to better understand the cellular mechanisms of gene regulation at the epigenetic and non-epigenetic levels, and be able to implement lincRNA use for diagnostics and therapies. In order to accomplish these goals we will integrate molecular and cell biology techniques with functional genomics approaches and in vivo studies. Importantly, the profiling of patient samples will reveal the relevance of our findings in human disease. Together, the functional study of lincRNAs will not only be crucial for developing improved diagnostics and therapies, but also will help a better understanding of the mechanisms that govern cellular network.

Champ scientifique

Régime de financement

ERC-SG - ERC Starting Grant

Institution d’accueil

FUNDACION PARA LA INVESTIGACION MEDICA APLICADA FIMA

Contribution de l’UE

€ 1 500 000,00

Adresse

AVENIDA DE PIO XII 55
31008 Pamplona
Espagne

Région

Noreste Comunidad Foral de Navarra Navarra

Type d’activité

Research Organisations

Contact administratif

Juan Manuel Saiz Abajo (Mr.)

Chercheur principal

Maite Huarte Martinez (Dr.)

Liens

Contacter l’organisation Site web

Coût total

Aucune donnée

Bénéficiaires (1)