Knockdown of lncRNA BDNF-AS suppresses neuronal cell apoptosis via downregulating miR-130b-5p target gene PRDM5 in acute spinal cord injury.

OBJECTIVE: The present study was designed to investigate the molecular mechanism and biological roles of lncRNA brain-derived neurotrophic factor antisense (lncRNA BDNF-AS) in acute spinal cord injury (ASCI).

METHODS: The rat model of ASCI and hypoxic cellular model were established to detect the expression of BDNF-AS, miR-130b-5p, PR (PRDI-BF1 and RIZ) domain protein 5 (PRDM5) and cleaved caspase 3 (c-caspase 3) using qRT-PCR and western blot. Basso, Beattie and Bresnahan (BBB) score was carried out to assess neurological function. Flow cytometry was used to determine the apoptosis of neuronal cells. The association among BDNF-AS, miR-130b-5p and PRDM5 were disclosed by RNA immunoprecipitation (RIP) assay, RNA pull-down assay and dual-luciferase reporter assay.

RESULTS: BDNF-AS, PRDM5 and c-caspase 3 expression were significantly upregulated, while miR-130b-5p was suppressed in the ASCI group and neuronal cells following hypoxia treatment. BDNF-AS knockdown inhibited neuronal cell apoptosis. Further studies indicated that BDNF-AS functioned as a competing endogenous RNA (ceRNA) by sponging miR-130b-5p in neuronal cells. Further investigations demonstrated that PRDM5 was a target of miR-130b-5p and BDNF-AS knockdown exerted anti-apoptotic effects via miR-130b-5p/PRDM5 axis.

CONCLUSION: The lncRNA BDNF-AS/miR-130b-5p/PRDM5 axis might be a promising therapeutic target for ASCI.