'Pseudogene' may play cancer role
A “pseudogene” previously thought to have no function may play a fundamental role in many cancers, new research suggests.
Scientists believe the DNA sequence regulates a well known “oncogene” linked to the disease.
Targeting the pseudogene with drugs that alter its effect may in future lead to new treatments.
Pseudogenes are short stretches of DNA that look like genes but differ in that they do not provide the coded instructions for making proteins.
Until recently they were lumped together with other non-protein making parts of the genetic code dismissed as “junk”.
Now scientists are learning that large areas of DNA once thought to have no function have a big influence on the activity of genes.
The cancer-linked pseudogene has a DNA sequence similar to the gene for PTEN, a protein believed to lie at the heart of many cancers, including those affecting the brain, prostate, womb, lung and breast.
PTEN normally acts as a cancer suppressor, but when defective can allow tumours to grow and spread.
The pseudogene cannot produce a protein of its own, but instead codes for short snippets of genetic material called micro-RNAs. These in turn have the power to control the activity of genes.
In this case, the pseudogene micro-RNAs affect PTEN in one of two ways, scientists found. They can either knock out the gene completely, causing it to shut down, or alter the levels of proteins it produces.
The research is reported today in the journal Nature Structural and Molecular Biology.
“We identified a new non-protein encoding pseudogene which determines whether the expression of PTEN is to be switched on or off,” said Per Johnsson, a member of the team from the Karolinska Institute in Sweden.
“What makes this case spectacular is that the gene only produces RNA, the protein’s template. It is this RNA that, through a sequence of mechanisms, regulates PTEN.”
The study showed that manipulating the pseudogene could alter the activity of PTEN and make tumours more responsive to conventional therapies.
“This means that we might one day be able to re-programme cancer cells to proliferate less, become more normal, and that resistance to chemotherapy can hopefully be avoided,” said Mr Johnsson.
“We also believe that our findings can be very important for the future development of cancer drugs. What we’re seeing here is just the tip of the iceberg.
“The human genome (genetic code) conceals no less than 15,000 or so pseudogene, and it’s not unreasonable to think that many of them are relevant to diseases such as cancer.”