A study of differential microRNA expression profile in migraine: the microMIG exploratory study

Abstract

Background Several studies have described potential microRNA (miRNA) biomarkers associated with migraine, but studies are scarcely reproducible primarily due to the heterogeneous variability of participants. Increasing evidence shows that disease-related intrinsic factors together with lifestyle (environmental factors), influence epigenetic mechanisms and in turn, diseases. Hence, the main objective of this exploratory study was to find differentially expressed miRNAs (DE miRNA) in peripheral blood mononuclear cells (PBMC) of patients with migraine compared to healthy controls in a well-controlled homogeneous cohort of non-menopausal women. Methods Patients diagnosed with migraine according to the International Classification of Headache Disorders (ICHD-3) and healthy controls without familial history of headache disorders were recruited. All participants completed a very thorough questionnaire and structured-interview in order to control for environmental factors. RNA was extracted from PBMC and a microarray system (GeneChip miRNA 4.1 Array chip, Affymetrix) was used to determine the miRNA profiles between study groups. Principal components analysis and hierarchical clustering analysis were performed to study samples distribution and random forest (RF) algorithms were computed for the classification task. To evaluate the stability of the results and the prediction error rate, a bootstrap (.632 + rule) was run through all the procedure. Finally, a functional enrichment analysis of selected targets was computed through protein–protein interaction networks. Results After RF classification, three DE miRNA distinguished study groups in a very homogeneous female cohort, controlled by factors such as demographics (age and BMI), life-habits (physical activity, caffeine and alcohol consumptions), comorbidities and clinical features associated to the disease: miR-342-3p, miR-532-3p and miR-758-5p. Sixty-eight target genes were predicted which were linked mainly to enriched ion channels and signaling pathways, neurotransmitter and hormone homeostasis, infectious diseases and circadian entrainment. Conclusions A 3-miRNA (miR-342-3p, miR-532-3p and miR-758-5p) novel signature has been found differentially expressed between controls and patients with migraine. Enrichment analysis showed that these pathways are closely associated with known migraine pathophysiology, which could lead to the first reliable epigenetic biomarker set. Further studies should be performed to validate these findings in a larger and more heterogeneous sample.

The Role of MicroRNA in Migraine: A Systemic Literature Review

“…Gallardo et al . ( 2023 ) assessed the levels of different miRNAs in non-menopausal women in comparison to healthy controls. The upregulation of 59 and downregulation of 132 different miRNAs have been shown.…”

“…Another interesting study was conducted by Gallardo et al . ( 2018 ), who analyzed the differential expression of multiple miRNAs in patients suffering from migraine in comparison to healthy individuals. The dysregulation of 41 miRNAs was observed in migraineurs in general.…”

The role of microRNAs in neurobiology and pathophysiology of the hippocampus

“…Dysregulations in functional and structural connections between hippocampus and other brain regions has been reported in migraine ( Planchuelo-Gomez et al, 2020 ; Zhu et al, 2021 ). The expression levels of miR-342-3p is elevated in migraine patients ( Gallardo Lopez et al, 2023 ). miR-342-3p regulates proliferation and apoptosis pathways in hippocampus via targeting BCL-2 expression ( Chen et al, 2021 ).…”