MicroRNA-140-5p inhibits cell proliferation and invasion by regulating VEGFA/MMP2 signaling in glioma

Tumour Biol. 2017 Apr;39(4):1010428317697558. doi: 10.1177/1010428317697558.

Abstract

Glioma is the most common primary malignant tumor of the central nervous system, which results in both a poor prognosis and outcome because of the aggressive progression of disease, growth and resistance to surgery, chemotherapy, and radiotherapy. MiR-140-5p is a small, non-coding single-stranded RNA molecule, which was previously studied in the settings of human tongue cancer, hepatocellular carcinoma, and colorectal cancer. However, detailed data that formally demonstrate the contribution of miR-140-5p to glioma development are missing. Similarly, relatively little is known about the relationship of miR-140-5p, vascular endothelial growth factor A, and matrix metalloproteinase-2 in glioma progression. In this study, we found that miR-140-5p expression was significantly decreased in glioma tissues and in the glioma cell-lines U87 and U251 as compared with non-cancerous brain tissues by quantitative real-time polymerase chain reaction. In addition, miR-140-5p inhibited glioma cell proliferation and invasion and promoted glioma cell apoptosis both in vivo and in vitro. Interestingly, while the expression levels of miR-140-5p were higher in glioma cells, the messenger RNA or protein expression levels of vascular endothelial growth factor A and matrix metalloproteinase-2 were lower in glioma cells as determined by quantitative real-time polymerase chain reaction, western blot assay, and immunohistochemistry. By contrast, downregulation in the expression levels of miR-140-5p augmented the messenger RNA and protein expression levels of both vascular endothelial growth factor A and matrix metalloproteinase-2. These findings suggested that miR-140-5p inhibited glioma proliferation and invasion by regulating the vascular endothelial growth factor A/matrix metalloproteinase-2 signaling pathway both in vitro and in vivo.

Keywords: MiR-140-5p; glioma; invasion; matrix metalloproteinase-2; proliferation; vascular endothelial growth factor A.

MeSH terms

  • Adult
  • Aged
  • Animals
  • Apoptosis / genetics
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glioma / genetics*
  • Glioma / pathology
  • Humans
  • Male
  • Matrix Metalloproteinase 2 / genetics*
  • Mice
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Signal Transduction / genetics
  • Vascular Endothelial Growth Factor A / genetics*
  • Xenograft Model Antitumor Assays

Substances

  • MicroRNAs
  • Mirn140 microRNA, human
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • MMP2 protein, human
  • Matrix Metalloproteinase 2