Biologists discover unique properties of MiR-93-5p microRNA in prostate cancer

Researchers at the International Laboratory of Microphysiological Systems of the HSE Faculty of Biology and Biotechnology investigated how different isoforms of the same microRNA influence gene function in prostate adenocarcinoma. The study found that in some cases, microRNAs can reinforce each other’s effects by targeting and suppressing the same genes. This finding offers a fresh perspective on the molecular mechanisms underlying tumour development and on the search for disease biomarkers. The results have been published in PeerJ.

MicroRNAs are small RNA molecules, typically 20–25 nucleotides long. They regulate gene expression by controlling how much protein is synthesised in a cell from a specific messenger RNA (mRNA) molecule. This regulation is mediated by a short sequence within the microRNA that can bind to a target mRNA if a complementary region is present. When binding occurs, translation of the mRNA is inhibited, leading to reduced gene expression. 

A single microRNA can exist in several variants, known as isoforms. Until recently, these isoforms were thought to function differently and regulate distinct sets of genes. However, researchers at HSE University have shown that this is not always the case. 

Biologists from the HSE Faculty of Biology and Biotechnology studied miR-93-5p, a microRNA that is highly expressed in oncological diseases, particularly prostate cancer. Moreover, higher expression levels are associated with more aggressive forms of cancer. 

The scientists conducted experiments in a cell line with overexpressing isoforms shifted by 3–4 nucleotides relative to the canonical miR-93-5p and found that these isoforms can suppress 54 genes. Analysis of patient data showed that these genes are also negatively correlated with the canonical form of miR-93-5p. This suggests that both the canonical miR-93-5p and its isoforms share the same mRNA targets. 

'It turns out that the microRNA miR-93-5p is unique. We found that its canonical form and isoforms enhance each other’s effects by suppressing the same genes. This may explain the consistent oncogenic role of miR-93-5p in prostate cancer and its potential as a biomarker of disease progression,' explains co-author of the study Anton Zhiyanov, Research Fellow at the Laboratory of Molecular Physiology of the HSE Faculty of Biology and Biotechnology.

Prostate cancer is the second most common cancer among men. According to the researchers, microRNAs could potentially serve as non-invasive biomarkers for the diagnosis and management of this disease, and a better understanding of gene regulation mechanisms may help identify new therapeutic targets.