LncRNA CASC2 inhibits astrocytic activation and adenosine metabolism by regulating PTEN in pentylenetetrazol-induced epilepsy model

Abstract

Growing evidence has indicated that long noncoding RNAs (lncRNAs) are closely implicated in the progress of epilepsy. However, the expression profile and potential function of long noncoding RNAs cancer susceptibility candidate 2 (lncRNA CASC2) in epilepsy are poorly studied. The aim of this study was to testify the influence of lncRNA CASC2 on epilepsy in rat and cell models of epileptic seizure. We adopted qRT-PCR on the hippocampus of rats following pentylenetetrazol (PTZ)-stimulated epilepsy. To further examine the correlation between lncRNA CASC2 and Phosphatase and tensin homolog (PTEN), we detected the effects of lncRNA CASC2 on PTEN expression. We found that lncRNA CASC2 and PTEN expression were positively correlated in PTZ-induced epileptic rat. Overexpression of lncRNA CASC2 prolonged the latency and reduced the frequency of epileptic seizure, suppressed the activation of astrocytes and the release of adenosine in epileptic rat, whereas downregulation of lncRNA CASC2 exhibited the opposite effects. Meanwhile, lncRNA CASC2 decreased the adenosine metabolism related proteins expression of p38, Equilibrative nucleoside transporter 1 (ENT1) and Adenosine Kinase (ADK). In PTZ-treated astrocytes, PTEN was found to be a direct target of lncRNA CASC2. Additionally, downregulation of PTEN attenuated the protective effect of lncRNA CASC2 overexpression in epileptic seizure. Our findings manifested the key role of lncRNA CASC2 in the occurrence of epilepsy by targeting PTEN, which provided a novel target for epilepsy therapy.

Keywords: Adenosine; Astrocyte activation; Epilepsy; PTEN; lncRNA CASC2.