Length does matter – looking at micro-RNAs to predict cancer and disease

A world-first study has shown ‘length does matter’ when using small molecules called microRNAs as potential biomarkers to detect and predict cancer and inflammatory diseases.

L-R: Ms Charlotte Nejad, Dr Genevieve Pepin and Dr Michael Gantier.

The study, published in the journal RNA, was led by Dr Michael Gantier and PhD student Ms Charlotte Nejad at Hudson Institute, together with collaborators from Monash University, Royal College of Surgeons in Ireland, University of Adelaide, Harvard University and Pasteur Institute.

“MicroRNAs are essential to life but are also involved in many diseases. Because microRNAs are secreted in fluids (such as blood and urine) and can be detected in very small quantities, they present a lot of potential for disease diagnostics,” Dr Gantier says.

Current research around the world is investigating the use of microRNAs as biomarkers for diagnosing or treating human cancer.

“Like all the building blocks that make up our body, microRNAs are constantly being renewed. However, little is known about microRNA longevity – the amount of time they ‘hang around’ in the body before being broken down and renewed,” Dr Gantier explains.

In the study, the team identified that during inflammation, the longer microRNAs appeared more prone to being degraded by the body. The persistence of shorter molecules, however, was not affected by inflammation.

What are MicroRNAs?

  • MicroRNAs (or miRNAs) are small molecules found in plants, animals and some viruses.
  • They are involved in switching different genes on and off.
  • The first micro-RNA was discovered in the early-1990s, but the research field has exploded in the past decade.
  • Current research is focused on identifying miRNAs as potential biomarkers for diagnosing or treating cancer, an area which needs further investigation and validation.
  • Evidence suggests that in cancer, miRNAs can modulate tumour growth by controlling genes which drive or supress the tumour.

“This suggests that the length of microRNAs controls their stability during disease, and although it’s not yet known whether this is important to the activity of microRNAs in diseases, this finding could lead to the development of novel biomarkers based on microRNAs,” he says.

Previous work from Dr Gantier has shown that the half-life for micro-RNAs (when half of the molecule has disappeared from the cells) is five days – but Dr Gantier says this could now differ based on length.

“The longevity – which we have found is linked to the length of microRNAs – is important because it affects their reliability as disease biomarkers that can be detected in fluids like blood or urine. In addition, since the longevity of long miRNAs is sensitive to simulation such as inflammation, specific detection of long microRNAs should inform on disease states.”

“MicroRNAs could help to detect the very early stages of cancer – and our research suggests that the specificity of the detection can be increased by several fold when also looking at microRNA length.

Publication: Nejad C, Pillman KA, Siddle KJ, Pepin G, Anko ML, McCoy CE, Beilharz T, Quintana-Murci L, Goodall GJ, Bracken CP and Gantier MP (2018) miR-222 isoforms are differentially regulated by type-I interferon. RNA. DOI: 10.1261/rna.064550.117 E Pub

Collaborators: Monash University, Royal College of Surgeons in Ireland, University of Adelaide, Harvard University and Pasteur Institute.

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