miR-495 reduces neuronal cell apoptosis and relieves acute spinal cord injury through inhibiting PRDM5

摘要

This study aims to investigate the role of miR-495 in neuronal cell apoptosis after acute spinal cord injury (ASCI). The ASCI rat model was established and the Basso, Beattie, and Bresnahan (BBB) score was assessed. miR-495, PR domain containing 5 (PRDM5), and Bcl-2 expressions were measured by qRT-PCR or western blotting. Neuronal cell line PC-12 was subjected to hypoxia condition to simulate the in vitro ASCI model. PC-12 cell apoptosis was measured by flow cytometry, and the interaction between miR-495 and PRDM5 was confirmed by dual luciferase reporter assay. Results showed that BBB score was significantly decreased in ASCI rats compared with sham rats. miR-495 expression was down-regulated in spinal cord tissue of ASCI rats and hypoxia-induced PC-12 cells, and PRDM5 protein level was up-regulated in spinal cord tissue of ASCI rats and hypoxia-induced PC-12 cells. miR-495 overexpression could reduce apoptosis of PC-12 cells, and up-regulated anti-apoptosis protein Bcl-2 protein level. Moreover, PRDM5 was a target of miR-495, and mRNA and protein levels of PRDM5 were negatively regulated by miR-495. miR-495 overexpression could reduce the hypoxia-induced PC-12 cell apoptosis, while PRDM5 overexpression abolished this inhibiting effect. The agomir-495 was injected into ASCI rats, and Bcl-2 protein level and BBB score were increased, but the PRDM5 overexpression reversed these results. Overall, we concluded that miR-495 could inhibit neuronal cell apoptosis and relieve acute spinal cord injury through inhibiting PRDM5.