# Circulating microRNAs in prostate cancer—Non-invasive biomarkers for diagnosis, prognosis, and therapy: A review

## TL;DR

This review explores how microRNAs in the blood could serve as non-invasive biomarkers for prostate cancer diagnosis, prognosis, and treatment monitoring.

## Contribution

The paper synthesizes evidence on miRNAs' role in prostate cancer and highlights their potential as non-invasive biomarkers with higher specificity than PSA.

## Key findings

- Circulating miRNAs like miR-21, miR-375, and miR-182-5p show greater specificity and stability than PSA for non-invasive prostate cancer management.
- Therapeutic approaches like antagomirs and CRISPR editing show preclinical promise but face challenges like off-target effects and delivery limitations.
- Standardized workflows and multicenter validation are needed to integrate miRNA-based tools into clinical practice.

## Abstract

Prostate cancer (PC) is a common malignancy driven by interacting genetic, environmental, and lifestyle factors, including hereditary mutations (BRCA1/2, HPC1, AR variants), premalignant lesions [proliferative inflammatory atrophy (PIA), prostatic intraepithelial neoplasia (PIN)], and Western dietary patterns. This narrative review aims to synthesize evidence on the role of microRNAs (miRNAs) in PC pathogenesis and clinical management across diagnosis, prognosis, therapy, and recurrence prediction. We searched PubMed/MEDLINE (2004–present) using predefined terms, screened reference lists, excluded outdated records, and prioritized biomarker studies with AUC ≥ 0.85. Current diagnostic pathways—digital rectal examination, prostate-specific antigen (PSA) testing, multiparametric MRI, and Gleason-based International Society of Urological Pathology (ISUP) grading—are complemented by molecular tools (4Kscore, PHI, SelectMDx, TMPRSS2–ERG, PCA3, ConfirmMDx). MiRNAs, key post-transcriptional regulators, contribute to PC via dysregulated biogenesis and modulation of androgen receptor (AR) signaling within an inflamed, remodeled tumor microenvironment. Circulating and exosomal miRNAs (notably miR-21, miR-375, and miR-182-5p) exhibit greater specificity and stability than PSA, enabling non-invasive diagnosis, risk stratification, treatment monitoring, and recurrence prediction. Therapeutic approaches—antagomirs, sponges, miRNA masks, and CRISPR editing—show preclinical promise, while chemical modifications [peptide nucleic acids (PNAs), locked nucleic acids (LNAs), C2′ modifications] improve stability and delivery but remain limited by biodistribution, tissue penetration, off-target effects, and immunogenicity. In conclusion, standardized workflows and multicenter validation, integrated with clinical and imaging data, are essential to translate miRNA-based tools into precision PC management.