The team, at the University of Michigan in Ann Arbor, identified THOR (Testis-associated Highly-conserved Oncogenic long noncoding RNA) while investigating an unexplored area of the genome harbouring a class of genes called long non-coding RNAs (ribonucleic acid) (lncRNAs). These genes do not contain information to make proteins, therefore they have long been regarded as 'junk' DNA. More recently, non-coding regions of the genome have proved to have diverse functions in health and disease.
The study, published in Cell, demonstrates that the newly discovered non-coding gene is highly conserved in different species, including humans, mice and zebrafish. 'Genes that are evolutionarily conserved are likely important for biological processes. The fact that we found THOR to be a highly conserved IncRNA was exciting,' said Dr Arul Chinnaiyan, who led the team.
When the researchers silenced THOR the tumour growth slowed down, instead THOR overexpression made tumours grow faster. Interestingly, THOR expression did not affect normal cells, suggesting a specific function of the gene in cancerous tissues.
THOR is highly expressed in tumours like melanoma and lung cancer and interacts with insulin-like growth factor-binding proteins, known to help stabilise RNA in the cells. 'If we perturb THOR function, we disturb the ability to stabilise RNA. This inhibits cell proliferation,' said Dr Chinnaiyan.
The research was conducted using in vitro systems and in animal models, so more studies are needed before the findings can be applied to patients. Dr Chinnaiyan suggested that THOR could be a good drug target - in the future, a therapeutic compound could be developed to 'knock-out' the gene, rendering it silent. The team hopes to develop this using a complementary sequence known as antisense oligonucleotide that can bind with THOR.