Extracellular vesicles from cerebrospinal fluid revealed changes in miR-19a-3p and miR-4516 expression in Slovene male suicides

Suicide is an important public-health concern, with more than 700,000 people dying by suicide yearly. It is a multifactorial phenomenon, shaped by the effects of sociodemographic, environmental and biological factors. The latter two factors can be linked through epigenetic studies, which examine differences in gene expression that are not due to changes in the DNA sequence itself. Epigenetic mechanisms include micro RNAs (miRNAs), which have a direct effect on already translated mRNA, leading to either decay or translational repression of the target mRNA. MiRNA molecules have been identified as cargo of extracellular vesicles (EVs) used by cells for long-distance communication, and pathophysiological changes in miRNA in brain cells may be reflected in cerebrospinal fluid (CSF) vesicles. In this study we investigated the presence and differential expression of selected miRNAs in EVs from the CSF of male suicide completers and controls. Western blot and nanoparticle tracking analyses confirmed the presence of small and medium sized EVs. Of the miRNA analyzed (miR-16-5p, miR-19a-3p, miR-34c-5p, miR-17-5p, miR-4286, miR-26b-5p, miR-381-3p, and miR-4516) miR-19a-3p and miR-4516 reached statistical significance with p-values of 0.0408 and 0.0168, respectively. Mir-4516 and miRNA-19a-3p have been previously studied in suicide, and target SLC6A4 and TNF-alpha expression, correspondingly. Approximately 70% of known miRNAs are expressed in the central nervous system, and therefore represent an important biomarker potential. Investigating the cargo of CFS and blood EVs would further support the identification of miRNAs with clinical use potential.