New Study Finds Association Between Small Noncoding RNAs and Cancer

A team of Canadian molecular biologists has established a link between some types of small noncoding RNAs (smRNAs) and certain cancers.

SmRNAs—RNA molecules that do not give rise to proteins but which may have other important functions in the cell—have been shown to be significantly enriched near the transcriptional start sites of genes. However, the functional relevance of these smRNAs has remained unclear, and they have not been associated with human disease.

Now, in a groundbreaking study, investigators associated with The Cancer Genome Atlas Project (Bethesda, MD, USA) have found that differences in the levels of specific types of noncoding RNAs can be used to distinguish between cancerous and noncancerous tissues. The Cancer Genome Atlas Project is a comprehensive and coordinated effort to accelerate the understanding of the molecular basis of cancer through the application of genome analysis technologies, including large-scale genome sequencing.

In prior cancer studies, these RNAs had been regarded as transcriptional "noise,” due to their apparent chaotic distribution. In contrast, in a study published in the February 1, 2014, issue of the journal EMBO reports investigators at the University of British Columbia (Vancouver, Canada) demonstrated the striking potential of certain smRNAs to distinguish efficiently between cancer and normal tissues and classify patients with cancer to subgroups of distinct survival outcomes.

They stressed that this potential to predict cancer status was restricted to a subset of smRNAs, which was encoded within the first exon of genes, highly enriched within CpG islands and negatively correlated with DNA methylation levels. In a CpG island, both cytosine and the guanine are found on the same strand of DNA or RNA and are connected by a phosphodiester bond.

"For many years, small non-coding RNAs near transcriptional start sites have been regarded as "transcriptional noise" due to their apparent chaotic distribution and an inability to correlate these molecules with known functions or disease," said senior author Dr. Steven Jones, professor of molecular biology at the University of British Columbia. "By using a computational approach to analyze small RNA sequence information that we generated as part of The Cancer Genome Atlas Project, we have been able to filter through this noise to find clinically useful information."

"The data from our experiments show that genome-wide changes in the expression levels of small noncoding RNAs in the first exons of protein-coding genes are associated with breast cancer," said Dr. Jones. "This is the first time that small noncoding RNAs near the transcription start site of genes have been associated with disease. Further work is required but based on our data we believe there is considerable diagnostic potential for these small noncoding RNAs as a predictive tool for cancer. In addition, they may help us understand better the mechanisms underlying oncogenesis at the epigenetic level and lead to potential new drugs employing small noncoding RNAs."

Related Links:
The Cancer Genome Atlas Project
University of British Columbia