MicroRNA-21 promotes neurite outgrowth by regulating PDCD4 in a rat model of spinal cord injury

Altered expression levels of microRNA-21 (miRNA-21) have been observed in a series of pathological processes, including cancer and central nervous system injury; however, the involvement of miRNA-21 in the molecular pathophysiology of spinal cord injury (SCI) has not been well documented. The present study examined the expression levels of miRNA-21 and its predicted target genes, programmed cell death 4 (PDCD4) and phosphatase and tensin homolog (PTEN), in rats using quantitative polymerase chain reaction and western blotting to further understand the role of miRNA-21 and the mechanisms underlying repair following SCI. The present study demonstrated that compared with uninjured spinal cords, miRNA-21 expression levels were significantly downregulated in injured spinal cords 4 and 8 h, and 1 day post-SCI, and were significantly upregulated after 3 and 7 days. Conversely, expression levels of PDCD4 and PTEN were significantly decreased at days 3 and 7 post-SCI compared with the control group. miRNA-21 overexpression in monolayer-cultured postnatal rat spinal cord neurons promoted neurite outgrowth and downregulated protein expression levels of PDCD4; however, PTEN protein expression levels were unaltered. To confirm that miRNA-21 directly targets PDCD4, a pRL-CMV luciferase reporter construct was used to detect miRNA-21 interactions with the PDCD4 3′-untranslated region. The results demonstrated that miRNA-21 decreased luciferase activity compared with a rat PDCD4 control reporter. The results of the present study suggested that increased miRNA-21 expression levels following SCI may promote the repair of injured spinal cords by inhibiting the expression of its target gene PDCD4.