Prohibitin blocks prostate cell growth but is lost when they become cancerous. In this project we aimed to restore normal growth to prostate cancer cells by increasing the levels of prohibitin. Our strategy was to trick the prostate cancer cells into doing this themselves, by reducing the levels of miR-27a which is a naturally occurring prohibitin inhibitor.
Through previous research funded by us, Professor Bevan identified a new potential drug target: a protein called prohibitin. Prohibitin is involved in slowing the growth of healthy prostate cells, and is found at lower levels in prostate cancer cells, which grow uncontrollably.
In this project, Professor Bevan wanted to investigate prohibitin further, and find a way to increase its levels in prostate cancer cells and potentially slow their growth.
It’s normally difficult to increase the levels of proteins in cells, however, the team found a way round this by targeting microRNAs, snippets of genetic material that are used naturally in the body to alter protein levels. By blocking one of these microRNAs, the team predicted it could have the knock-on effect of increasing prohibitin levels.
The team found that one microRNA in particular, called miR27a, is important in controlling prohibitin levels, and also affects how prostate cancer cells divide and generate energy.
They developed several chemicals designed to inhibit miR27a, and therefore increase prohibitin levels and affect prostate cancer cell growth. Excitingly, they found the most effective of these reduced the size of prostate cancer tumours in mice.
This project is a promising first step to develop a new drug for advanced prostate cancer. However, before it reaches men, the team will need to continue testing their anti-miR27a chemical in mice.
In the meantime, a researcher who worked with Professor Bevan on this project has been awarded funding from us to investigate the effect of miR27a on energy production in prostate cancer cells. This could support the development of an anti- miR27a drug, and provide new leads for other drug targets.
Given the promising effect of her anti-microRNA chemical, Professor Bevan is now looking at other microRNAs that might be involved in prostate cancer, and could provide the key to a better treatment or way to diagnose the disease in the future.
There is potential for one or more new therapies based on inhibition of microRNAs that can affect prostate cancer cell growth – with fewer side-effects and toxicities than are associated with conventional therapies.
Institution - Imperial College London
Researcher - Professor Charlotte Bevan
Grant award - £243,893
Duration - 2011-2014
Reference - PG10-25