A press release has been published on the atypical synergistic effect of miR-93-5p microRNA isoforms in prostate cancer

A press release has been released on the HSE website (https://www.hse.ru/news/science/1152167635.html) based on an article about the unique properties of miR-93-5p microRNA (published in the journal PeerJ https://peerj.com/articles/20642/). HSE researchers have discovered an atypical behavior of oncogenic miR-93-5p microRNA in prostate cancer. It turned out that its various isoforms do not change the spectrum of target genes, but rather enhance each other's effects.

MicroRNAs play a key role in the post-transcriptional regulation of gene expression by binding to complementary regions of messenger RNA (mRNA) and suppressing translation (protein synthesis). In the process of microRNA biogenesis, their precursor molecules are often inaccurately dissected, which leads to the formation of isoforms (isomyrnas). Traditionally, it is believed that 5' isoforms that have a shift in the seed region, which is critical for binding, should have a completely different set of mRNA targets compared to the canonical microRNA form.
A team of HSE scientists (Anton Zhiyanov, Ivan Kirillov, Roman Suvorov, Diana Maltseva, and Alexander Tonevitsky) focused on studying miR-93-5p— a microRNA with proven oncogenic activity that is highly expressed in prostate cancer. To identify the targets of the 5' isoforms, the researchers used a shRNA-based hyperexpression system in the PC-3 prostate adenocarcinoma cell line.
Analysis of the RNA sequencing data revealed an overlap between the targetomes of canonical miR-93-5p and its 5' isoforms, the sequence of the seed region of which is shifted by 3 and 4 nucleotides. This overlap is explained by the simultaneous presence of binding sites for both canonical and shifted seed regions in the same mRNA molecules. Thus, the heterogeneity of the 5' end in the case of miR-93-5p does not lead to target divergence. Instead, the canonical microRNA and its isoforms work synergistically, providing excessive and more severe suppression of common transcripts. This may explain the stable oncogenic role of miR-93-5p in prostate cancer and its promise as a potential biomarker of disease progression.
The results were published on February 16 in the journal PeerJ.