Identification of key potassium channel genes of temporal lobe epilepsy by bioinformatics analyses and experimental verification

Lin-Ming Zhang; Ling Chen; Yi-Fei Zhao; Wei-Mei Duan; Lian-Mei Zhong; Ming-Wei Liu

doi:10.3389/fneur.2023.1175007

Identification of key potassium channel genes of temporal lobe epilepsy by bioinformatics analyses and experimental verification

Front Neurol. 2023 Jul 7:14:1175007. doi: 10.3389/fneur.2023.1175007. eCollection 2023.

Authors

Lin-Ming Zhang^{1

2}, Ling Chen^{1

2}, Yi-Fei Zhao^{1

2}, Wei-Mei Duan^{1

2}, Lian-Mei Zhong^{1

2}, Ming-Wei Liu³

Affiliations

¹ Department of Neurology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
² Yunnan Provincial Clinical Research Center for Neurological Disease, Kunming, Yunnan, China.
³ Department of Emergency, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.

Abstract

One of the most prevalent types of epilepsy is temporal lobe epilepsy (TLE), which has unknown etiological factors and drug resistance. The detailed mechanisms underlying potassium channels in human TLE have not yet been elucidated. Hence, this study aimed to mine potassium channel genes linked to TLE using a bioinformatic approach. The results found that Four key TLE-related potassium channel genes (TERKPCGs) were identified: potassium voltage-gated channel subfamily E member (KCNA) 1, KCNA2, potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11), and KCNS1. A protein-protein interaction (PPI) network was constructed to analyze the relationship between TERKPCGs and other key module genes. The results of gene set enrichment analysis (GSEA) for a single gene indicated that the four TERKPCGs were highly linked to the cation channel, potassium channel, respiratory chain, and oxidative phosphorylation. The mRNA-TF network was established using four mRNAs and 113 predicted transcription factors. A ceRNA network containing seven miRNAs, two mRNAs, and 244 lncRNAs was constructed based on the TERKPCGs. Three common small-molecule drugs (enflurane, promethazine, and miconazole) target KCNA1, KCNA2, and KCNS1. Ten small-molecule drugs (glimepiride, diazoxide, levosimendan, and thiamylal et al.) were retrieved for KCNJ11. Compared to normal mice, the expression of KCNA1, KCNA2, KCNJ11, and KCNS1 was downregulated in the brain tissue of the epilepsy mouse model at both the transcriptional and translational levels, which was consistent with the trend of human data from the public database. The results indicated that key potassium channel genes linked to TLE were identified based on bioinformatics analysis to investigate the potential significance of potassium channel genes in the development and treatment of TLE.

Keywords: WGCNA; bioinformatics analyses; potassium channel genes; target drugs; temporal lobe epilepsy.