MicroRNAs and suicidality: a systematic review and bioinformatic evaluation

Introduction: Suicide is a leading global cause of mortality (~800,000 deaths annually) driven by complex biological and environmental determinants; although microRNAs (miRNAs) regulate gene expression implicated in psychiatric disorders, their contributions to suicidality-related phenotypes remain incompletely defined. Methods: We searched Web of Science, PubMed, Scopus, Embase, and Ovid through July 14, 2025, for human case-control studies comparing individuals with suicidality-related phenotypes to non-suicidal controls. Risk of bias was assessed with the Newcastle-Ottawa Scale. Differentially expressed miRNAs were compiled and analyzed to identify brain-specific gene targets, followed by pathway and disease enrichment. Results: Of 1,437 records screened, 13 studies met inclusion criteria, encompassing 285 suicidal participants and 291 controls. Across studies, 43 unique miRNAs showed significant differential expression between cases and controls. Three miRNAs-miR-30a, miR-30e, and miR-218-were consistently dysregulated across brain samples from individuals who died by suicide. Bioinformatic analyses indicated that these miRNAs converge on brain-expressed targets and processes relevant to psychiatric biology. Enrichment highlighted pathways involved in transcriptional regulation, forkhead box O (FoxO) signaling, Ras-associated protein-1 (Rap1) signaling, long-term depression, and dopaminergic synapse function. Conclusion: miR-30a, miR-30e, and miR-218 emerge as recurrently altered miRNAs in suicide and may serve as mechanistic mediators and candidate biomarkers. Mapping their brain-specific targets and enriched pathways suggests actionable avenues for risk stratification and therapeutic development. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier PROSPERO CRD42024582398.