Noncoding DNA sequence may play a role in ageing and cancer

A sequence of repetitive noncoding DNA that varies considerably in length between humans, has been shown to play a role in ageing and cancer.

An international group of scientists looked at a region of DNA called VNTR2-1. They found deleting this region reduced tumour growth and contributed to cell ageing. Researchers discovered this region controls the activity of an enzyme called telomerase which is responsible for the production of telomeres, regions of DNA found at the end of chromosomes that protect them from damage or fusing with the ends of other strands.

'Almost 50 percent of our genome consists of repetitive DNA that does not code for protein. Our study describes that one of those units actually has a function in that it enhances the activity of the telomerase gene.' said Professor Jiyue Zhu, professor of pharmaceutical sciences at Washington State University, Pullman.

Telomeres get shorter each time a cell divides, and when it becomes too small, the cells age and die. But in certain types of cells, including some cancer cells, telomerase activity ensures the length does not shorten each time the cell divides and the cell does not age and die as it would normally. This is one reason cancer cells grow uncontrollably and form tumours.

'Our findings are telling us that this VNTR2-1 sequence contributes to the genetic diversity of how we age and how we get cancer.' Professor Zhu added.

In this study, published in Proceedings of the National Academy of Sciences, took a number of approaches. Deleting the VNTR2-1 region in cancer cells in human cell lines and mice resulted in shorter telomere length, halted tumour growth and cell ageing.

The US researchers also conducted a study looking at the length of the VNTR2-1 sequences in participants from the Georgian Centenarian Study, which followed a group of white and African American people aged 100 or above. The sequence lengths varied from shorter to much longer with some as short as 53 repeats in the region, to some as long as 160 repeats. Very short sequences were only found in African American participants.

A shorter sequence of VNTR2-1 does not necessarily lead to a shorter lifespan. This is as telomerase activity is lower, making telomere length in the cells shorter and less likely to develop into cancer cells.

We know that oncogenes—or cancer genes—and tumour suppressor genes don't account for all the reasons why we get cancer. Our research shows that the picture is a lot more complicated than a mutation of an oncogene and makes a strong case for expanding our research to look more closely at [noncoding DNA].' said Professor Zhu.