Methylation of the miR-126 gene associated with glioma progression

Fam Cancer. 2016 Apr;15(2):317-24. doi: 10.1007/s10689-015-9846-4.

Abstract

Gliomas are the most common and the most malignant brain tumors, accouting for 45-55% of all intracranial tumors. The incidence of glioma worldwide is about 6-12 per 100,000. Recently, several studies showed that the activation of the oncogenes and the inactivation and/or loss of the tumor suppressor genes, especially for miRNA-21, let-7 and so on, are the most primary molecule event in gliomas. MicroRNAs (miRNAs) are a class of endogenously expressed small noncoding RNAs which are usually 21-23 nucleotides long. miRNAs regulate gene expression and play important roles in a variety of physiological and pathological processes, such as cell proliferation, differentiation and apoptosis. To date, Growing evidence has shown that mi RNAs are frequently dysregulated in human cancers and can act as both tumor suppressors and oncogenes. Along with the discovery of micro RNA, more and more research focusing on its relationship with glioma was carried out to investigate the biological features of glioma and to provide experimental evidence for glioma mechanism. In the present study, we aimed to verify the miRNA-126 down-regulation which showed in the results of glioma tissue miRNAs chip and discuss the miRNA-126 methylation in patients with glioma. A total of 50 samples from patients with glioma and 20 control samples from patients with cerebral trauma were included in this study. The expression levels of the miR-126 gene were detected using quantitative polymerase chain reaction (PCR), and the methylation status of miR-126 was examined using methylation-specific PCR-denaturing high-performance liquid chromatography (MSP-DHPLC). The expression level of miRNA-126 was found to be significantly higher in the control group (0.6134 ± 0.1214) than in the glioma group (0.2771 ± 0.1529; P < 0.05). The expression was also significantly elevated in low-grade gliomas (0.3117 ± 0.1474) compared with high-grade gliomas (0.1582 ± 0.1345; P < 0.05). In addition, increased methylation of miR-126 was found in 40% of glioma patients in our study (20/50 cases), resulting in significantly decreased miR-126 expression (0.1715 ± 0.1376; P < 0.05). Our results indicate that we verified successfully the miRNA-126 down-regulation phenomenon in patients with glioma which showed in the results of glioma tissue miRNAs chip and the miRNA-126 down-regulation through methylation in patients with glioma. So we could say that epigenetic modification is a crucial mechanism for controlling the expression of miR-126 in glioma.

Keywords: Down-regulation; Glioma; Methylation; miR-126.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / pathology
  • Case-Control Studies
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genetic Association Studies
  • Glioma / genetics*
  • Glioma / pathology
  • Humans
  • Male
  • Methylation
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Promoter Regions, Genetic
  • Reverse Transcriptase Polymerase Chain Reaction / methods

Substances

  • MIRN126 microRNA, human
  • MicroRNAs