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MicroRNAs and suicidality: a systematic review and bioinformatic evaluation
Mahdi Malekpour1,2, Mohammadreza Akbari3, Mobin Fallah Tafti4
1Research Center for Psychiatry and Behavioral Sciences, Shiraz University of Medical Sciences, Shiraz, Iran.
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.
Insights
Three microRNAs (miRNAs) show consistent dysregulation in suicide brains. These miRNAs, miR-30a, miR-30e, and miR-218, may serve as biomarkers for suicide risk and therapeutic targets.
Area of Science:
- Neuroscience
- Genetics
- Psychiatry
Background:
- Suicide is a global health crisis with complex biological underpinnings.
- MicroRNAs (miRNAs) are crucial gene regulators implicated in psychiatric disorders.
- The specific role of miRNAs in suicidality remains to be fully elucidated.
Purpose of the Study:
- To systematically review and analyze microRNA (miRNA) expression in individuals with suicidality-related phenotypes.
- To identify specific miRNAs and their potential biological pathways associated with suicide.
- To explore the utility of miRNAs as biomarkers and therapeutic targets for suicide prevention.
Main Methods:
- A comprehensive literature search was conducted across major scientific databases.
- Human case-control studies comparing suicidal individuals to non-suicidal controls were included.
- Differentially expressed miRNAs were identified, and bioinformatic analyses were performed for target and pathway enrichment.
Main Results:
- Thirteen studies involving 285 suicidal participants and 291 controls met the inclusion criteria.
- Forty-three unique miRNAs were found to be differentially expressed.
- miR-30a, miR-30e, and miR-218 were consistently dysregulated in brain samples from individuals who died by suicide.
Conclusions:
- miR-30a, miR-30e, and miR-218 are recurrently altered miRNAs in suicide.
- These miRNAs may act as mechanistic mediators and candidate biomarkers for suicidality.
- Target and pathway analysis suggests potential for risk stratification and therapeutic development in suicide prevention.
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