Aberrant Expression of miR-323a-5p in Patients with Refractory Epilepsy Caused by Focal Cortical Dysplasia

Genet Test Mol Biomarkers. 2017 Jan;21(1):3-9. doi: 10.1089/gtmb.2016.0096. Epub 2016 Nov 8.

Abstract

Background: Epilepsy remains one of the most common clinical neurological disorders. About a third of patients with epilepsy are refractory to drug treatment, mainly as a result of focal cortical dysplasia (FCD). In this study, we analyzed the aberrant expression of microRNAs (miRNAs) in the cortex and plasma of FCD patients.

Methods: Cortical samples were collected from nine patients with refractory epilepsy caused by FCD who underwent surgery, and from eight volunteers (control group) undergoing emergency surgery for hypertensive cerebral hemorrhage. miRNA expression in the cortex was detected by microarray analysis and miR-323a-5p expression levels in the cortex were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). We also collected plasma samples from 30 patients with refractory epilepsy caused by FCD and from 23 healthy controls, and compared differential expression of miR-323a-5p in the plasma using qRT-PCR.

Results: miRNA microarray analysis showed that expression of miR-323a-5p was upregulated in the FCD group compared with the control group, and miR-323a-5p expression levels in the cortex analyzed by qRT-PCR supported those obtained by microarray analysis. Plasma levels of miR-323a-5p were significantly higher in patient plasma compared with the healthy controls, as determined by qRT-PCR. Furthermore, expression of miR-323a-5p was positively correlated with the duration of epilepsy (p = 0.014) and seizure frequency (p = 0.043). The effectiveness of surgery in patients with FCD was significantly poorer in patients with high plasma levels of miR-323a-5p compared with those with low levels.

Conclusions: The expression of miR-323a-5p was significantly elevated in the cortex and plasma of FCD patients. These results suggest that abnormal expression of miR-323a-5p could be used for improving the current diagnosis of FCD and monitoring treatment responses in patients with FCD.

Keywords: focal cortical dysplasia; miR-323a-5p; plasma; refractory epilepsy.

MeSH terms

  • Adult
  • Case-Control Studies
  • Drug Resistant Epilepsy / blood
  • Drug Resistant Epilepsy / genetics*
  • Drug Resistant Epilepsy / metabolism
  • Female
  • Gene Expression Profiling
  • Humans
  • Male
  • Malformations of Cortical Development / blood
  • Malformations of Cortical Development / genetics*
  • Malformations of Cortical Development / metabolism
  • MicroRNAs / biosynthesis*
  • MicroRNAs / blood
  • MicroRNAs / genetics
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis

Substances

  • MIRN323 microRNA, human
  • MicroRNAs