Disease- and headache-Specific miRNA signatures and predicted targets in the peripheral blood mononuclear cells of migraineurs. Migraine small RNA-Seq

MicroRNAs (miRNAs) are short, non-coding RNAs that play an important regulatory role in post-transcriptional gene repression. Specific miRNAs may become future druggable targets or biomarkers in several human disorders including chronic pain conditions. Initial evidence suggests miRNA's’ contribution to migraine pathomechanism, however, more data areis needed.This study aimed to investigate patterns of differential microRNA (miRNA) expressions in peripheral blood mononuclear cells (PBMCs) of migraineurs in a self-controlled manner during and between attacks. In addition, we aimed to predict possible mRNA targets. Thus, small RNA-sequencing, microRNA (miRNA)-mRNA target prediction and network construction, and Gene Ontology analysis were performed on samples of 16 female migraineurs and 15 healthy participants samples. Predictions were validated at the mRNA level, based on a comparison of node strength values and differentially expressed mRNA data.In interictal samples compared to healthy ones 27 miRNAs were found to be differentially expressed, e.g. hsa-miR-5189-3p, hsa-miR-96-5p, hsa-miR-3613-5p, hsa-miR-542-3p, and hsa-miR-99a-3p. Top differentially expressed miRNAs during headache attacks are as follows: hsa-miR-3202, hsa-miR-7855-5p, hsa-miR-6770-3p, hsa-miR-1299, hsa-miR-409-5p. Our validation process in mRNA target prediction brought to light several genes related to an immune and inflammatory response supplemented with oxidative stress and mitochondrial dysfunction.We demonstrated a considerable difference in PBMC miRNA signature between migraineurs and healthy controls, more pronounced in the headache-free period. These results suggest the role of inflammatory components in headache generation.