MicroRNA-138-5p regulates the development of spinal cord injury by targeting SIRT1

MicroRNAs (miRs) play an important role in the development and progression of spinal cord injury (SCI). The role of miR-138-5p in SCI was investigated in the present study. The anti-inflammatory effects of miR-138-5p and underlying mechanisms were investigated in an SCI rat model and in vitro model. Reverse transcription-quantitative PCR (RT-qPCR) was used to examine the expression of miR-138-5p in the SCI in vivo and in vitro models, as well as patients with SCI; it was found that miR-138-5p was significantly upregulated in SCI. Bioinformatics and dual-luciferase reporter assays were performed to predict and confirm the binding sites between miR-138-5p and the 3′untranslated region of sirtuin 1 (SIRT1). Then, the expression of SIRT1 was detected via RT-qPCR and western blotting, indicating downregulation of SIRT1 in SCI. PC12 cells were transfected with miR-138-5p inhibitor, inhibitor control or miR-138-5p inhibitor + SIRT1 small interfering RNA for 48 h, and then subjected to lipopolysaccharide (100 ng/ml) treatment for 4 h. Then, MTT assay, flow cytometry and ELISA experiments were performed to analyze cell viability, apoptosis, and the levels of tumor necrosis factor-α, interleukin (IL)-1β and IL-6. Findings suggested that downregulation of miR-138-5p increased PC12 cell viability, inhibited cell apoptosis and attenuated proinflammatory responses, which may result in amelioration of SCI. However, all these effects were reversed by SIRT1 knockdown. Finally, it was observed that miR-138-5p altered the related protein expression of the PTEN/AKT pathway. These results indicated that miR-138-5p could regulate inflammatory responses and cell apoptosis in SCI models by modulating the PTEN/AKT signaling pathway via SIRT1, thus playing an important role in the development of SCI. Collectively, the present study demonstrated that miR-138-5p may be a novel therapeutic target for the treatment of SCI.