Functional and mechanistic roles of long intergenic non-coding RNAs in cancer.
Mammalian cells encode thousands of RNA molecules that are structurally similar to protein-coding genes-they are long, subject to splicing, polyadenylated, transcribed by RNA Pol II, and have conserved promoters and exonic structures-but have coding capacity. Although thousands exist, only a few of these intergenic non-coding RNAs (lincRNAs) have been characterized and have shown potent biological functions of gene expression through various epigenetic and non-epigenetic mechanisms. Significantly, their expression patterns suggest that some lincRNAs are involved in critical cellular pathways in cancer, such as the p53 pathway.
I have explored this association, demonstrating that p53 induces the expression of numerous lincRNAs. One of them, the so-called lincRNA-p21, is directly induced by p53 to play a pivotal role in the p53 response, and is required to globally repress genes that interfere with the induction of apoptosis by p53. My results, together with 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 level, and to achieve using lincRNA for diagnostics and treatments. In order to achieve these goals, we will combine molecular and cell biology techniques with functional genomic approaches and in vivo studies. Most importantly, profiling of patient samples will reveal the relevance of our findings to human disease.
Taken together, the functional study of lincRNAs will not only be crucial for the development of better diagnostics and therapeutics, but will also help to better understand the mechanisms that govern cellular networks.
- Convocation: HORIZONTE 2020
- Reference: CANCERLINC
- Start date: January 1, 2011
- End date: December 31, 2018
- Funder: Programa del Consejo Europeo de Investigación - Starting Grant
- Grant: 1.500.000 €
- Nature of project: International