Fig. 8

Neuroinflammation-related network analysis revealed MyD88 one of the most relevant predicted targets for miR-669c-3p. Panel a represents the workflow adapted in order to detect new genes significantly associated with miR-669c-3p. MiR-669c-3p was used as an input to query miRTarBase and TargetScan databases. Both experimentally validated targets from miRTarBase and TargetScan genes associated with miR-669c-3p were subsequently evaluated in STRING interaction database. Then a network was created, composed by the interactions between aforementioned targets depicted as nodes, as well as the interactions between TargetScan and miRTarBase targets including only those with high confidence (score ≥ 900). Finally, a pathway enrichment analysis of each connected component of the network was applied using the R package ReactomePA and only pathways enriched with an adjusted p value < 0.01 were retrieved. Panel b shows the results of pathway enrichment analysis prior (gray bars) and after (orange bars) the addition of interactions between TargetScan and miRTarBase targets in the network construction according to the workflow. When the network includes within-group interactions, only the connected component containing MyD88 (TargetScan target) and TLR6 (miRTarBase target) significantly increases the number of enriched neuroinflammatory pathways (23 Toll-like-receptor pathways). Panel c features the network obtained with adapted workflow. Diamond-shape green nodes are TargetScan targets directly connected to miRTarBase targets represented as rectangle-shape blue nodes. Rectangle-shape green nodes are the TargetScan targets connected to blue nodes due to the within-group interactions (green-green). Each subnetwork is one of the connected components enriched in pathways associated with neuroinflammation