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

Mol Med Rep. 2017 Sep;16(3):2522-2528. doi: 10.3892/mmr.2017.6862. Epub 2017 Jun 27.

Abstract

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.

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / genetics*
  • Cells, Cultured
  • Down-Regulation
  • Female
  • Gene Expression Regulation*
  • MicroRNAs / genetics*
  • Neuronal Outgrowth*
  • PTEN Phosphohydrolase / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Cord / metabolism
  • Spinal Cord / pathology
  • Spinal Cord Injuries / genetics*
  • Spinal Cord Injuries / pathology
  • Transcriptome
  • Up-Regulation

Substances

  • Apoptosis Regulatory Proteins
  • MicroRNAs
  • Pdcd4 protein, rat
  • mirn21 microRNA, rat
  • PTEN Phosphohydrolase
  • Pten protein, rat