Targetome profile of hsa-miR-93-5p is resistant to isoform formation in prostate adenocarcinoma

PeerJ. 2026. Vol. 14. Article e20642.

Zhiyanov A., Kirillov I., Suvorov R., Maltseva D., Tonevitsky A.

MicroRNAs (miRNAs) and their isoforms, known as isomiRs, are important regulators of tumorigenesis that act as post-transcriptional modulators of gene expression. Among these, 5’-isomiRs—generated through imprecise cleavage during miRNA biogenesis—exhibit altered seed regions compared to their canonical counterparts, potentially leading to distinct targetomes. Consequently, 5’-isomiRs may exert biological functions that differ substantially from those of the corresponding canonical miRNAs. Despite growing recognition of their potential significance, the functional roles of 5’-isomiRs remain largely uncharacterized for most miRNAs. In this study, we investigated the targetome divergence between canonical miRNAs and their 5’-isomiRs, focusing on hsa-miR-93-5p, a miRNA with a well-established oncogenic role in prostate adenocarcinoma. Target transcripts of the 5’-isomiRs were identified using a shRNA-based overexpression system. Bioinformatic analysis revealed a substantial overlap between the targets of the 5’-isomiRs and the canonical miRNA. This overlap was attributed to the co-occurrence of both canonical and shifted seed motifs within the same mRNA targets. Notably, hsa-miR-93-5p ranked among the top miRNAs with a relatively high number of targets transcripts containing both seed motifs, suggesting a unique dual-targeting capacity.

Keywords: miR-93-5p, Dual targeting, 5’-isomiR targets, Seed region, miR-93-5p, 5’-изомиРНК мишени, Seed регион

Publication based on the results of: Microfluidic models (2025)