Long non-coding RNA Mirt2 relieves lipopolysaccharide-induced injury in PC12 cells by suppressing miR-429

Abstract

Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) play important roles in the pathogenesis of spinal cord injury (SCI). This study investigated the effects of lncRNA Mirt2 and miR-429 on lipopolysaccharide (LPS)-induced injuries in PC12 cells. Serum samples were collected from 36 patients with SCI and the healthy controls. The expression of lncRNA Mirt2 in serum samples was measured by qRT-PCR. The in vitro model of SCI was established by treating PC12 cells with LPS. The effects of lncRNA Mirt2 and miR-429 on the cell model were evaluated by CCK-8 assay, flow cytometry, western blot, qRT-PCR, and ELISA. Further, the activation of NF-κB and p38MAPK pathways was tested by western blot. LPS induced obvious cell injuries in PC12 cells, as cell viability was reduced, apoptosis rate was increased, caspase-3 and -9 were cleaved, and the release of TNF-α and IL-6 was induced. lncRNA Mirt2 was up-regulated in LPS-stimulated PC12 cells and serum samples derived from SCI patients. Overexpression of lncRNA Mirt2 protected PC12 cells against LPS-induced injuries. Further studies found that lncRNA Mirt2 acted as the molecular sponge of miR-429 and miR-34a-5p. lncRNA Mirt2 did not protect PC12 cells when miR-429 was overexpressed. Moreover, the inhibitory effects of lncRNA Mirt2 on NF-κB and p38MAPK pathways were abolished when miR-429 was overexpressed. lncRNA Mirt2 exerts protective effects in an in vitro model of SCI by down-regulating miR-429. This study shed light on the treatment of SCI by using the lncRNA-miRNA regulation network.

Keywords: Apoptosis; Inflammation; Mirt2; Spinal cord injury; miR-429.