Is Noncoding RNA a Culprit in Prostate Cancer?

Noncoding RNA appears to be involved in the epigenetic regulation of prostate cancer, according to findings published in Nature Genetics.

“Our research looked at genetic variations associated with prostate cancer and we found that about half of those genetic variations may function through noncoding genes rather than the protein-coding genes,” said senior study coauthor Housheng Hansen He, PhD, of the Princess Margaret Cancer Centre, University Health Network, in Toronto, Ontario, Canada, in an interview. “Noncoding RNA have very important functions in driving prostate cancer development and progression.”

The vast majority of the human genome does not encode proteins and was long dismissed as “junk” DNA-meaningless detritus that had accumulated over millions of years. But epigeneticists like Dr. He, are finding that the noncoding RNA expressed by these regions actually play important and complex regulatory roles for genes in the protein-encoding exome. In other words, noncoding RNA genes function as tuning dials and switches for the activation and regulation of other, protein-encoding genes.

Little is known about how exactly the 123 genomic risk regions associated with prostate cancer contribute to tumor development, Dr. He noted. But the new study suggests that many of these regions involve epigenetic regulatory roles for noncoding RNA.

Dr. He and colleagues used integrative analyses of noncoding RNA transcriptome, genome, and single nucleotide polymorphisms from prostate tumor genome-wide association studies to identify candidate long noncoding RNAs (lncRNAs) associated with prostate cancer progression.

They then more closely studied the “top hit” among these candidate lncRNAs, PCAT1, which was previously shown to be elevated in patients with prostate cancer and to modulate several prostate cancer tumorigenesis pathways, including BRCA2 and MYC.

The team found that PCAT1 apparently “functions as a kind of glue” that binds protein complexes together, in order to epigenetically upregulate genes involved in tumorigenesis, Dr. He explained.

A risk-associated single nucleotide polymorphism (SNP), rs7463708, modulates chromatin binding of ONECUT2 transcription factor, which the researchers found interacts with AR and the PCAT1 promoter in a manner that upregulates PCAT1 during prolonged androgen therapy.

The researchers plan next to similarly explore the functions of the other 44 genes.

The findings might hasten development of prognostic biomarkers for personalized treatment decision-making, Dr. He noted.