MicroRNA-23b attenuates the H2O2-induced injury of microglial cells via TAB3/NF-κB signaling pathway

Apoptosis of microglia is one of the most important pathophysiologic changes after spinal cord injury (SCI). Recently, microRNAs (miRNAs) have been reported to play a crucial role in the regulation of neuronal apoptosis. However, the exact role and underlying mechanisms of miRNAs in the regulation of microglial apoptosis remain unclear. We first performed miRNA microarray to analyze the miRNA expression patterns in a rat SCI model. The expression of microRNA-23b (miR-23b) in spinal cord after contusion SCI was determined by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). BV-2 cells were exposed to H 2 O 2 conditions to establish an in vitro model of SCI. Then, the effects of miR-23b on the apoptosis were investigated through both gain- and loss-of-function studies in this cellular model of SCI. Also, the expression of the main proteins in NF-κB signaling was assessed by Western Blot. Furthermore, bioinformatics analysis was used to predict the target of miR-23b in BV-2 cells, which was validated with a dual-luciferase reporter assay, qRT-PCR, and Western blot analysis. The expression of TGF-β-activated kinase 1 binding protein 3 (TAB3) in cells was overexpressed by transfection with pcDNA-TAB3, and the effects of TAB3 overexpression on miR-23b-mediated apoptosis were detected. Here, we demonstrated that miR-23b was significantly down-regulated in SCI rat model. We also found that the expression level of phosphorylated p65 (p-p65) protein was increased in the SCI rat model. Subsequently, treatment of BV-2 cells with H 2 O 2 decreased the levels of miR-23b and activated NF-κB pathway in a dose dependent manner. Furthermore, overexpression of miR-23b inhibited the BV-2 apoptosis and NF-κB activation, while miR-23b inhibition enhanced the apoptosis and NF-κB activation induced by H 2 O 2 . Moreover, our data showed TAB3, an upstream positive regulator of the NF-κB pathway, was proven to be a target of miR-23b in BV-2 cells. Most importantly, we demonstrated that overexpression of miR-23b attenuated the apoptosis by inhibiting the expression of TAB3. These findings suggested that miR-23b protected BV-2 cells from apoptosis by modulating the NF-κB pathway and could serve as a new strategy for the treatment of SCI.