Downregulation of microRNA‑155 by preoperative administration of valproic acid prevents postoperative seizures by upregulating SCN1A.

Abstract

The risk of seizure is increased following brain surgery such as cranioplasty. Patients with seizures that are treated with valproic acid (VPA) may have a decreased risk of further seizures. To verify microRNA (miR)‑155 as a potential biomarker for the occurrence of seizures, reverse transcription quantitative polymerase chain reaction (RT‑qPCR) was used. Computational analysis and luciferase reporter assay was performed to identify the putative target of miR‑155. RT‑qPCR and western blot analyses were used to determine the expression level of miR‑155, sodium voltage‑gated channel α subunit 1 (SCN1A) mRNA and protein. RT‑qPCR analysis indicated that miR‑155 levels in patients who experienced seizures increased 2.45‑fold compared with patient who did not experience seizures, indicating miR‑155 may be a potential biomarker for the occurrence of seizures. SCN1A was identified as a target gene of miR‑155; the luciferase reporter assay revealed a negative regulatory relationship between miR‑155 and SCN1A. The expression of SCN1A mRNA of patients receiving VPA was higher compared with the control group patients. Furthermore, the expression levels of SCN1A mRNA and protein were reduced or elevated following transfection with miR‑155 mimics or inhibitors, respectively, compared with the scramble control. Furthermore, a concentration‑dependent effect of miR‑155 on the expression of SCN1A was observed. In conclusion, miR‑155 may be associated with the risk of seizure and SCN1A may be a target gene of miR‑155. Downregulation of microRNA‑155 by preoperative administration of VPA may prevent postoperative seizure by upregulating the expression of SCN1A.