MiR-1202 Exerts Neuroprotective Effects on OGD/R Induced Inflammation in HM Cell by Negatively Regulating Rab1a Involved in TLR4/NF-κB Signaling Pathway.

Recent studies have shown that the level of miR-1202 in peripheral blood is closely related to brain activity and cognitive function in patients with depression, and it is involved in glioma pathological progress. However, the correlation between miR-1202 and neuroinflammation has not been reported. The expressions of miR-1202 and small GTP-ase Rab1a at mRNA level were detected in oxygen-glucose deprivation (OGD)/reoxygenation (R) induced human microglial cells (HM cells) by RT-qPCR at different time points within 48 h. Dual luciferase report assay and immunofluorescence staining were performed to confirm whether Rab1a was the potential target of miR-1202. The toll-like receptor 4 (TLR4)/nuclear factor kappa beta (NF-κB) signal related proteins (TLR4, P65, p-P65, IκBa) and the downstream pro-inflammation factors pro-IL-1β, pro-IL-18, as well as the inflammation factors interleukin-1β (IL-1β) and interleukin-18 (IL-18) were detected by western-blotting. The expression level of TLR4 on cell surface was detected by flow cytometry. Down-regulation of miR-1202 and up-regulation of Rab1a were found in OGD/R induced HM cells. In addition, miR-1202 was identified to directly target Rab1a and down-regulate its expression. Moreover, over-expression of miR-1202 suppressed the activation of TLR4/NF-κB inflammatory signaling pathway. Rab1a can increase the expression level of TLR4 on the surface of OGD/R induced HM cells. MiR-1202 exerts neuroprotective effect by negatively regulating its target protein Rab1a, which can inactivate TLR4/NF-κB-involved inflammatory signaling pathway in OGD/R induced HM cells. These findings provide potential therapeutic targets for ischemic stroke.