When viruses visit us, sometimes they leave a part of themselves behind.
Some of these foreign DNA fragments, quietly hidden in our genomes, can be passed down through generations. They were long thought to be inactive, but we have since learned that these stowaway sequences can turn on again and wreak havoc.
A research team led by University of Colorado bioinformatician Atma Ivancevic found that cancer cells can use some of these zombie viruses to their advantage.
“Our study shows that modern diseases may be significantly influenced by ancient viral infections that, until recently, only a few researchers had noticed.” Say Edward Chuong, genome biologist and senior author.
Long denigrated as ‘junk’ DNA, we owe it to ourselves to fragments of viral remnants. Endogenous retrovirus (ERV) because it facilitated our existence as mammals. Evolution of the placentaWithout them we would not be human.
But like most things, ERVs come with costs, costs we’re only just beginning to understand.
“We know that cancer cells express a lot of genes that should not be turned on, but no one knows what actually turns them on.” explain Chuong. “Many of the switches that turn them on turn out to be derived from this ancient virus.”
Ivansevich and her team analyzed published data sets on the epigenomes of 21 different types of cancer and were surprised to find that a particular ERV family called long terminal repeat 10 (LTR10) was highly active. The original virus infected our primate ancestors about 30 million years ago.
Functional studies in colon cancer cell lines have revealed that LTR10 regulates the expression of genes with established roles in tumorigenesis.
When the undead LTR10 gene was turned off in human colon cancer cells and mice, genes known to drive cancer growth, including XRCC4, which is involved in treatment resistance, were also turned off. This allowed therapies that reduce tumors in mice to work better.
Ivancevic and his team concluded that LTR10 acts as an epigenetic switch that controls these genes.
Cancer cells appear to use discarded viral parts to change gene expression patterns throughout the tumor, and just one type of retrovirus regulates as many as 70 cancer-related genes.
Ivancevic and his team were able to determine which genes LTR10 regulates in tumor cells, but they could not directly confirm whether those genes were associated with the growth and spread of specific cancers. They recommend further studies in patient-derived organoids to make such connections.
Researchers speculate that as we age and our defenses break down, more of these zombie virus fragments will resurface, causing other health problems later in life.
Slowly but surely, scientists are turning their attention to the more obscure aspects of our biology that lie behind this complex situation.
This study was published in Advancement of Science.
