MicroRNAs are short pieces of genetic material that pass on important messages in cells. Just one microRNA can interact with several genes, having a substantial knock-on effect on which proteins – and how many of them – are produced in a cell.
Broadly speaking there are two distinct but overlapping themes in the study of microRNAs in cancer: their use as potential biomarkers, and their potential as new targets for drug treatment. Biomarkers
A biomarker is a molecule you can measure, for example using a blood test, to give clues about the existence, extent, or characteristics of disease. Because increased levels of particular microRNAs can be detected in the blood, and increases in the levels of microRNAs can correlate with cancer, a simple blood test could in theory help in diagnosing some cancers, or dividing them up into different groups potentially requiring different types of treatment. Even if increased levels of microRNAs are only a by-product of a cancer – rather than actual drivers of the disease – such a test would still be useful in the clinic.
For example, a recent study
led by Professor Gareth Morgan here at the Institute of Cancer Research in London showed that some people with myeloma, a cancer of immune cells in the bone marrow, have higher levels of a set of microRNAs in their blood than others with the disease. These myeloma patients were more likely to die of their disease than patients with lower levels of these RNAs. That means that in the future, a blood test that measured their levels could help separate patients more accurately into groups based on their risk of developing fatal myeloma – which in turn could help inform the treatments they receive. New drugs?
However, the study of microRNAs is about much more than the search for new possible biomarkers. We know that they could also be playing an active role in cancer, because they can interact with several different genes at once. Are microRNAs one of the weapons cancer uses to grow and spread? Could ‘shooting the messenger’ by blocking microRNAs halt the progression of cancer? A new research paper
published in prestigious journal Cancer Cell
shows that the answer to both question is, at least in colorectal cancer, yes. The lead author of the important study was new ICR team leader Dr Nicola Valeri, who carried out much of the work in his previous role at the University of Glasgow, and the study was led by internationally renowned cancer scientist and microRNA expert Professor Carlo Croce, from Ohio State University Comprehensive Cancer Center.
Looking in particular at microRNAs in colorectal cancer, the study used a series of painstaking experiments to prove that marked increases in the level of one particular microRNA are not simply a bystander event to cancer-causing genetic changes – this one microRNA actually drives the development of cancer, through its effects on multiple cancer genes.
In mice and samples of human cancer cells, Dr Valeri’s team showed that levels of microRNA 135b were very substantially raised in colorectal cancer. This microRNA acted as a messenger on behalf of a set of cancer-causing genes or gene mutations – APC, PI3KCA, SRC and p53 – to block the expression of genes TGFBR2 and DAPK1, which are involved in cell proliferation and avoiding cell death, and block FIH, which governs yet another set of genes that help prevent cancer cells from spreading to new parts of the body. APC, PI3KCA, SRC and p53 were acting through microRNA 135b – using it as a middle man to drive cancer cells into more advanced, dangerous forms. In mice, inhibiting this one microRNA reduced tumour growth.
The discovery is exciting because it shows that putting microRNA 135b out of action – with new drugs – could slow down colorectal cancer by blocking the activation of several cancer-causing genes at once. A drug to block the effects of microRNA 135b is not a reality yet, but this new study is a step forward in our efforts to discover new and innovative ways of tackling cancer.
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