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

## TL;DR

This study explores how the microRNA hsa-miR-93-5p and its isoforms regulate gene expression in prostate cancer, finding that they share many targets due to overlapping seed motifs.

## Contribution

The study reveals that hsa-miR-93-5p and its 5’-isomiRs share target transcripts due to co-occurring seed motifs, suggesting a dual-targeting mechanism.

## Key findings

- 5’-isomiRs of hsa-miR-93-5p share many targets with the canonical miRNA due to overlapping seed motifs in mRNAs.
- hsa-miR-93-5p ranks among miRNAs with the highest number of transcripts containing both canonical and shifted seed motifs.
- The study highlights a unique dual-targeting capacity of hsa-miR-93-5p in prostate adenocarcinoma.

## Abstract

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.