This review summarizes current evidence on the biological, diagnostic, prognostic, and therapeutic significance of microRNAs (miRNAs/miRs) in prostate cancer (PCa). Dysregulated miRNA networks contribute to PCa initiation, progression, metastasis, and therapy resistance by regulating androgen receptor signaling, proliferation, apoptosis, epithelial-mesenchymal transition, angiogenesis, hypoxia signaling, bone tropism, and castration-resistant evolution. Oncogenic miRNAs, including miR-21, miR-93, miR-9, miR-181a, and miR-182, promote malignant phenotypes through survival, TGF-β, PI3K/AKT, MAPK, HIF-1α, and EMT-associated pathways, whereas tumor-suppressor miRNAs, including the miR-34 family, miR-145, miR-122, and miR-382, restrict proliferation, stem-like traits, invasion, metastasis, and treatment resistance. Circulating, urinary, and exosomal miRNAs have potential as minimally invasive biomarkers for PCa detection, risk stratification, recurrence monitoring, metastatic risk prediction, and assessment of castration-resistant disease. Multi-miRNA panels, such as miR-375-3p/miR-182-5p, miR-34b-3p/miR-361-5p/miR-200c-3p, and miR-200c/miR-605/miR-135a/miR-433/miR-106a, may outperform individual markers by capturing multiple biological pathways and reducing single-marker variability; however, most remain at the discovery or validation stage rather than routine clinical implementation. Translation requires standardized sample handling, hemolysis control, reproducible RNA extraction, validated normalization strategies, assay harmonization, locked thresholds, and multicentre prospective validation against PSA, imaging, histopathology, and established risk models. High-throughput platforms, including qRT-PCR, microarray, next-generation sequencing, and nCounter digital counting, support miRNA discovery and validation but differ in sensitivity, specificity, cost, throughput, bioinformatic complexity, and clinical deployability. Therapeutically, anti-miRs, miRNA mimics, sponges, masks, CRISPR-based approaches, and nanocarrier-assisted delivery systems provide experimental strategies for inhibiting oncogenic miRNAs or restoring tumor-suppressor miRNAs. Preclinical evidence supports miR-21 inhibition and replacement of miR-34a, miR-145, miR-15a/miR-16-1, miR-124, and miR-205. Still, clinical translation is limited by off-target effects, immune activation, delivery efficiency, endosomal escape, tumor heterogeneity, pharmacokinetics, toxicity, scalability, and manufacturing reproducibility. Overall, miRNAs provide mechanistic insight into PCa heterogeneity and offer promising opportunities for precision diagnosis, prognosis, and therapy, with the most realistic near-term application being integration of validated miRNA panels with PSA, multiparametric MRI, pathology, and multi-omic or AI-assisted risk models.
