MiR-33-5p alleviates spinal cord injury in rats and protects PC12 cells from lipopolysaccharide-induced apoptosis.

Abstract

MicroRNAs (miRNAs) exert critical effects in spinal cord injury (SCI). The miR-33-5p level is found to be lower in rats with SCI compared with that in control (untreated) and sham-operated (laminectomy but no contusion) rats. Therefore, we investigated the biological functions of miR-33-5p and related mechanisms in SCI pathogenesis and development. An in vivo SCI model and a lipopolysaccharide (LPS)-induced cell model of SCI were established. A downregulated level of miR-33-5p in experimental SCI and in LPS-treated PC12 cells was revealed by reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR). MiR-33-5p upregulation alleviated the leakage of the blood-spinal cord barrier (BSCB) induced by SCI and improved the neurological functions of SCI rats, as evidenced by the Basso, Beattie, and Bresnahan (BBB) scores and Evans blue staining. The regulatory relationship between miR-33-5p and Rps6kb1 was verified by luciferase reporter assays, which demonstrated that miR-33-5p bound to the Rps6kb1 3'UTR. Moreover, as MTT assays and flow cytometry showed, the suppressive effects of miR-33-5p upregulation on cell apoptosis were attenuated by Rps6kb1 upregulation. In conclusion, miR-33-5p ameliorates SCI in rats and inhibits the LPS-induced apoptosis of PC12 cells.