MicroRNA profiling in postmortem brain and plasma exosomes: Biomarker perspective of suicidality

Abstract

IntroductionSuicide is a leading cause of death. Although research on the biological aspects of suicide is accumulating, there is no testable biomarker to assess suicidality. miRNAs, small non-coding RNAs, have been implicated in synaptic plasticity, genetic susceptibility to stress and coping to stress response. Because of the presence of microRNAs in circulating body fluids, miRNAs can not only be used as regulators of disease pathologies but also in prognosis and treatment response.ObjectivesWhether miRNAs can be used as biomarker for suicidality.AimsTo examine miRNA expression in brain of suicide victims and in plasma exosomes of suicidal individuals.MethodsmicroRNA expression was studied in prefrontal cortex of depressed suicide subjects and healthy normal controls. Role of microRNAs in synaptic plasticity was studied by examining total and synaptonerosomes. microRNA expression was also studied in plasma exosomes of depressed non-suicide and depressed suicide subjects and healthy normal controls.ResultsWe found a global down–regulation of miRNAs in depressed subjects (21 miRNAs significantly down-regulated). Many of them were synaptically enriched and encoded at nearby chromosomal loci, shared motifs within the 5’-seeds, and shared putative mRNA targets. In addition, we found a dramatic reorganization of microRNAs in a coordinated and cohesive fashion in depressed subjects. We also detected changes in miRNAs in plasma exosomes of depressed suicide subjects that corresponded to microRNA changes in prefrontal cortex.ConclusionOur study provides critical evidence that microRNAs play a major role in suicide pathophysiology and that these microRNAs can be reliably used as peripheral biomarker.Disclosure of interestThe author declares that he has no competing interest.