After eight years spent analyzing the human genome and its many regulatory molecules, a team from Northwestern University has discovered a seemingly foolproof self-destruct pathway that can be used to destroy any type of cancer cell.
The mechanism involves the creation of small RNA molecules (siRNAs) that interfere with multiple genes essential to the proliferation of fast-growing, malignant cells, but have little effect on normal, healthy cells.
Through insights gained in two recent studies, research leader Marcus Peter and his colleagues have characterized the fatal cascade of events these siRNA molecules trigger – dubbed DISE, for Death By Induced Survival gene Elimination – and identified the six-nucleotide-long sequences that are needed for such activity.
When examining nucleotide sequences of the many noncoding (meaning they don’t get translated into proteins) RNA molecules our bodies naturally produce to selectively inhibit gene expression, they found that DISE-associated sequences are present at one end of many tumor suppressing RNA strands. Another investigation revealed the sequences are also found embedded in protein-coding sequences throughout the genome.
"We think this is how multicellular organisms eliminated cancer before the development of the adaptive immune system, which is about 500 million years old," Peter said in a statement last year. "It could be a fail-safe that forces rogue cells to commit suicide. We believe it is active in every cell protecting us from cancer."
But they still needed to determine how the body produces free siRNAs that can trigger DISE. This breakthrough came in another new study, published last month in eLife, wherein Peter and his team observed the process by which our cells chop a larger RNA strand – that codes for a cell death cycle protein called CD95L – into multiple siRNAs.