Non-Coding ‘Junk’ DNA May Suppress Development Of Breast Cancer

According to new research conducted at the University of Bath and the University of Cambridge in the UK, so-called ‘junk’ DNA could be responsible for preventing breast cancer. The study – published in the journal, Nature Communications – is just one of many recent publications that challenge the idea that these non-coding regions of the human genome have no purpose.

While the human genome is composed of approximately three meters of DNA, completion of the Human Genome Project in 2001 revealed that only two percent of that DNA contains coding sequences for proteins. While much of this DNA had previously been considered to be of no purpose, recent evidence suggests these sequences are transcribed into non-coding RNA.

Though this non-coding RNA has been identified, scientists are now left to postulate what function it might have in the cell if it is not used to synthesize proteins. Current techniques make this pursuit difficult for researchers as knock-outs often damage the DNA sequences, leading to confounded results.

The current study details the discovery of a stretch of non-coding DNA that is transcribed into a short segment of non-coding RNA, and seems to be responsible for preventing cells from entering a state of uncontrolled, cancerous growth. According to the researchers, the hope is that their discovery will be valuable in the development of new oncology therapies.

“The number of cells in our body are balanced by the level at which cells replicate and replace the ones that die,” said Dr. Adele Murrell, a researcher at the University of Bath’s Department of Biology & Biochemistry, and the leader of the study. “Sometimes the switches that control this growth get stuck in the ‘on’ position, which can lead to cancer.”

“As the tumour grows and the cancer cells get crowded, they start to break away from the tumour, change shape and are able to burrow through tissues to the bloodstream where they migrate to other parts of the body, which is how the cancer spreads,” Murrell continued. “This process is called metastasis and requires a whole network of genes to regulate the transformation of cell shape and mobilization.”

“In our study we’ve identified that GNG12-AS1, a strand of non-coding RNA, prevents the growth switch getting stuck and suppresses metastasis,” she said. “The specific genomic region where this non-coding RNA is located often gets damaged in breast cancer patients — this control is removed and the cancer cells spread.”

Murrell and her team identified two distinct mechanisms by which the non-coding RNA prevents healthy cells from turning cancerous. The non-coding sequence regulates the levels of a close-by gene – known as DIRAS3 – involved in cell replication. The RNA fragment also acts to suppress a host of genes that are responsible for encouraging cells to undergo shape changes and metastasize.

The researchers used small interfering RNAs (siRNAs) to prevent transcription of the non-coding RNA sequence being studied, or to destroy the RNA directly after it was constructed. While both techniques involving siRNA silencing resulted in cells with altered shapes and metastatic capabilities, only the first approach – wherein transcription was prevented – resulted in misregulation of DIRAS3.

“Only a tiny fraction of our DNA contains actual genes, and we know that at least some of the bits in between – often dismissed as ‘junk’ – play important roles in controlling how genes get switched on and off at the right time and in the right place,” said Dr. Kat Arney, science communication manager at Cancer Research UK, the organization that funded the research. “Research like this is helping is to unpick the precise details about how these regions work, shedding light on their potential role in the development of cancer and pointing towards new approaches for tackling the disease.”