Significance of miR-196b in Tumor-Related Epilepsy of Patients with Gliomas

ObjectivesSeizure is a common presenting symptom of primary brain tumors. There are no published studies regarding the roles of MicroRNA (miRNA) in tumor-related epilepsy. The authors set out to correlate miR-196b expression in low-grade glioma patients with pre-operative seizures and post-operative seizure control. MethodsTwenty-three patients with WHO grade II astrocytomas and 83 similar patients for independent validation were included. Follow-up visits regarding seizure prognosis were scheduled at 6 months. MiRNA profiling was used to identify differentially expressed miRNAs. The most important miRNA was determined by quantitative reverse-transcriptase polymerase chain reaction (q-PCR) in the validation cohort. Gene ontology (GO) analysis and whole genome mRNA profiling was performed to investigate the underlying biological processes. ResultsArray results showed that 30 miRNAs were overexpressed and 10 miRNAs were underexpressed (with more than 2 fold change) in patients with pre-operative seizures. MiR-196b was validated in the independent validation cohort. Patients with good seizure prognosis exhibited low levels of miR-196b expression compared with those who had poor seizure prognosis in the group without pre-operative seizures. Biological processes that relate to transcription and cell cycles were over-represented in the miR-196b-associated gene expression signature. MiR-196b-associated gene expression profiling was characterized by enrichment of genes usually involved in cell proliferation. ConclusionsWe have provided the first evidence that expression of miR-196b was associated with the occurrence of pre-operative seizures in low-grade gliomas, and may predict seizure prognosis in patients without pre-operative seizures. Targeted treatments that decrease endogenous levels of miR-196b might represent novel therapeutic strategies.