Dysregulation of microRNA-128 expression in WHO grades 2 glioma is associated with glioma-associated epilepsy: Down-regulation of miR-128 induces glioma-associated seizure

Epilepsy Res. 2016 Nov:127:6-11. doi: 10.1016/j.eplepsyres.2016.08.005. Epub 2016 Aug 11.

Abstract

Objective: Approximately 80% of glioma patients will experience at least one seizure activity during the course of the disease, and because the etiology of glioma-related seizure is most likely multifactorial and complex, it remains poorly understood. MicroRNAs are a class of small noncoding RNAs that function as critical gene regulators. MicroRNA-128 was found to be decreased in glioblastoma, and knockout of the microRNA-128a gene could induce epilepsy in mice. Based on the Chinese Glioma Genome Atlas and previous study, we hypothesized that dysregulation of miR-128 expression may play a role in the pathogenesis of TAE in low-grade glioma.

Methods: Fifty-three low-grade glioma samples were analyzed for the expression levels of miR-128 using qRT-PCR, and candidate targets of miR-128 (Cacnge2, GRIK3, and GRIN2D) were detected by the 3'-UTR luciferase reporter assay. Four other miRs (miR-9, miR-192a, miR-92a, and miR-451) that showed dysregulation of glioblastoma in the CGGA data were also analyzed.

Results: The microRNA-128 expression levels were down-regulated in low-grade glioma tissue (t-test; p=0.009). Dysregulation of miR-128 expression in low-grade glioma is associated with glioma-associated epilepsy (p=0.006). No statistical significance of miR-9, miR-192a, miR-92a, and miR-451 was found to be associated with LGG.

Conclusion: Our results here, together with other recent lines of evidence, indicate that miR-128 is an extremely attractive target for therapy in glioma patients with seizure.

Keywords: Dysregulation; Epilepsy; Glioma; Seizure; miR-128.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Brain / metabolism*
  • Brain / pathology
  • Brain / surgery
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Brain Neoplasms / surgery
  • Down-Regulation
  • Epilepsy / metabolism*
  • Epilepsy / pathology
  • Epilepsy / surgery
  • Glioma / metabolism*
  • Glioma / pathology
  • Glioma / surgery
  • Humans
  • MicroRNAs / metabolism*
  • Neoplasm Grading
  • World Health Organization

Substances

  • MIRN128 microRNA, human
  • MIRN192 microRNA, human
  • MIRN451 microRNA, human
  • MIRN92 microRNA, human
  • MicroRNAs
  • Mirn129 microRNA, human