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Updated: Feb 24, 2026
miRNA Expression Analyses in Prostate Cancer Clinical Tissues
Published on: September 8, 2015
Targetome profile of hsa-miR-93-5p is resistant to isoform formation in prostate adenocarcinoma
Anton Zhiyanov1, Ivan Kirillov1, Roman Suvorov1
1Faculty of Biology and Biotechnology, Higher School of Economics, Moscow, Russia.
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.
Insights
This study explores how 5'-isomiRs, miRNA variants, target genes differently than canonical microRNAs (miRNAs). Findings reveal significant overlap in targets due to shared seed motifs, suggesting a dual-targeting role for hsa-miR-93-5p.
Area of Science:
- Molecular Biology
- Genetics
- Cancer Research
Background:
- MicroRNAs (miRNAs) and their isoforms, isomiRs, regulate gene expression and are implicated in tumorigenesis.
- 5'-isomiRs, arising from imprecise miRNA processing, possess altered seed regions, potentially leading to distinct target interactions compared to canonical miRNAs.
- The functional impact of 5'-isomiRs remains largely unexplored for most miRNAs.
Purpose of the Study:
- To investigate targetome divergence between canonical miRNAs and their 5'-isomiRs.
- To characterize the functional roles of 5'-isomiRs, focusing on hsa-miR-93-5p in prostate adenocarcinoma.
Main Methods:
- Utilized a shRNA-based overexpression system to identify target transcripts of 5'-isomiRs.
- Employed bioinformatic analysis to compare targetomes of canonical miRNAs and their 5'-isomiRs.
- Focused on hsa-miR-93-5p, a known oncogenic miRNA in prostate cancer.
Main Results:
- Identified a substantial overlap in target transcripts between canonical hsa-miR-93-5p and its 5'-isomiRs.
- Attributed target overlap to the co-occurrence of canonical and shifted seed motifs within the same mRNA targets.
- hsa-miR-93-5p demonstrated a high number of target transcripts containing both seed motifs, indicating a potential dual-targeting capacity.
Conclusions:
- 5'-isomiRs can share targets with canonical miRNAs due to conserved and variant seed regions.
- hsa-miR-93-5p exhibits a unique capacity for dual targeting, influencing tumorigenesis through both canonical and isomiR-mediated pathways.
- Further research into 5'-isomiR functions is crucial for understanding gene regulation and cancer development.
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