Describing miRNA–target networks of miR22-3p and miR145-5p involved in neuroinflammation

Background: MicroRNAs (miRNAs) control biological processes and inflammatory responses of microglia. Their post-transcriptional capabilities play important roles in limiting neuroinflammation in multiple sclerosis (MS).

Methods: The N9 microglia cell line was classically activated in vitro by lipopolysaccharide (LPS). IL-6 and TNF-α production was determined with ELISA to confirm LPS activation, and miRNA expression was quantified using cDNA and qPCR at six and 24 hours. Validated targets found in silico from miRTarBase were then compared to the Gene Expression Omnibus (GEO) dataset: GSE183038 to analyse gene expression modifications in microglia during neuroinflammation.

Results: miR-22-3p was significantly upregulated with LPS activation at six hours with a relative quantification of 0.068 ± 0.004 when compared to the control of 0.052 ± 0.003 (p=0.004) at six hours. Targets of miR-22-3p were significantly upregulated (Ass1, Arpc5, Ywhaz and Max), and downregulated (Cdc25c, Irf8 and Hdac4 (p<0.001)). Ass1 is most dysregulated, with a log fold expression of 0.631 (p = 6.80E-20).

Conclusion: miR-22-3p was significantly upregulated at six hours and validated genes were found to be dysregulated. Regulation of miR-22-3p expression is a promising therapeutic strategy for MS treatment.