Reduced expression of microRNA-497 is associated with greater angiogenesis and poor prognosis in human gliomas

Hum Pathol. 2016 Dec:58:47-53. doi: 10.1016/j.humpath.2016.04.022. Epub 2016 Aug 25.

Abstract

MicroRNA (miR)-497 plays a tumor-suppressive role in several malignancies and is involved in glioma invasiveness and resistance to chemotherapy. To add to the knowledge of the clinical significance of miR-497 in human gliomas, quantitative real-time polymerase chain reaction was performed to detect the expression of miR-497 in 110 pairs of freshly prepared glioma and nonneoplastic brain tissues. Then the associations of miR-497 expression with various clinicopathological characteristics and overall survival of glioma patients were estimated statistically. Gain-of-function assays were also performed to examine the role of miR-497 in glioma angiogenesis. The expression of miR-497 in human glioma tissues was significantly lower than in nonneoplastic brain tissues (P<.001). In addition, low miR-497 expression was significantly associated with advanced World Health Organization grade (P<.001) and low Karnofsky performance scores (P=.02). Moreover, the survival of glioma patients with low miR-497 expression was dramatically shorter than that of patients with high miR-497 expression (P=.001). Forced expression of miR-497 in glioma cells inhibited tube formation by cocultured human brain microvascular endothelial cells. We also found that miR-497 overexpression in glioma cells led to decreased expression of vascular endothelial growth factor. In conclusion, miR-497 may be a favorable prognostic marker in human gliomas, in part by being a negative regulator of angiogenesis, implying its potential as a therapeutic target for this cancer.

Keywords: Angiogenesis; Clinicopathological features; Glioma; Prognosis; miR-497.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Brain Neoplasms / blood supply
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Child
  • Coculture Techniques
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glioma / blood supply
  • Glioma / genetics*
  • Glioma / metabolism
  • Glioma / pathology
  • Humans
  • Kaplan-Meier Estimate
  • Karnofsky Performance Status
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Neoplasm Grading
  • Neovascularization, Pathologic*
  • Real-Time Polymerase Chain Reaction
  • Transfection
  • Vascular Endothelial Growth Factor A / metabolism
  • Young Adult

Substances

  • Biomarkers, Tumor
  • MIRN497 microRNA, human
  • MicroRNAs
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A