Long noncoding RNA, Gene Regulation and Cancer
The human genome codes for thousands of mysterious RNA molecules that are structurally identical to protein genes (they are long, transcribed by RNA polymerase II, polyadenylated and subject to splicing). Nevertheless, they lack any coding ability. Though there are thousands of long, non-coding RNAs (lncRNA), they are not well studied. We have shown that lncRNA is involved in cellular pathways that are critical for cancer, such as p53, and we have demonstrated that the p53 tumor suppressor induces expression of several lncRNAs. For example, we identify lincRNA-p21, which suppresses gene expression in the p53 pathway and promotes apoptosis (Huarte et al., Cell, 2010), and linc-Pint, an lncRNA with tumor-suppression properties that induces epigenetic modifications in response to p53 (Marín-Béjar et al., Genome Biology, 2013). And we demonstrate that a group of p53-regulated lncRNAs constitute a tumour suppressor signature with high diagnostic power (Sánchez et al, Nature Communications, 2014). Therefore, lncRNA plays a key role in several tumor-suppression and oncogenic pathways and represents a paradigm that was unknown in tumor transformation. However, its mechanisms and biological functions remain unexplored.
Our laboratory investigates how lncRNA contributes to gene regulation and expression mechanisms in cancerous cells. In order to achieve this, we apply the most advanced epigenomic and functional genomic technologies combined with molecular biology techniques, in vivo studies and analysis of patient samples. Our studies are aimed at making it possible to apply lncRNA to the diagnosis and treatment of cancer, in addition to helping better understand the mechanisms that govern cell networks.
*(Huarte et al., Cell, 2010)
**(Marín-Béjar et al., Genome Biology, 2013)
***(Sánchez et al., Nature Communications 2014)