Effect of circ RNA_0017178 on a mouse model of epilepsy induced by pentatetrazide

Acta Universitatis Medicinalis Anhui     font:big middle small

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Authors:Mao Jian,Wen Pingping, Sun Hongying, Zhang Shuya, Meng Chenxi, Zhang Jia

Keywords:circ_0017178;epilepsy;differential expression;bioinformatics analys;apoptosis

DOI:10.19405/j.cnki.issn1000-1492.2023.12.014

〔Abstract〕 Objective To investigate the possible mechanism of circ RNA in the pathogenesis of epilepsy. Methods In this study, circRNA expression profiles in peripheral venous blood of epileptic patients and healthy controls were studied by using circRNA gene chip technology, and differentially expressed circrnas were screened. Bioinformatics databases such as circPrimer, circMir and TargetScan were used to analyze its possible role in epilepsy and adenovirus vector was constructed. Thirty male adult C57BL/6 mice were randomly divided into control group, empty vector group and circ_0017178 overexpressed group(10 mice/group). Normal saline, empty plasmid adenovirus vector and circ_0017178 overexpressed adenovirus vector were injected into the hippocampus of the three groups respectively. The change of animal behavior of mice in each group was observed after the establishment of pentetrazole epilepsy model, and the apoptosis of hippocampal tissue cells of mice in each group was analyzed by Tunel staining. Results The results of gene microarray showed that circ_0069272, circ_0033065, circ_0017178, circ_0073442, circ_0033063 and circ_0049415 in epilepsy group were up-regulated significantly compared with the control group. And circ_0083773, circ_0088262, circ_0016396 decreased significantly. Circ_0017178 might be the most associated with epilepsy. Through bioanalysis, circ_0017178 might regulate 39 epilepsy genes by combining 20 miRNA and possess potential m6A, IRES and ORF1 binding sites. In the experiment of pentatetrazole epileptic mice, compared with the empty carrier group and the control group, the latency period of epilepsy in the circ_0017178 overexpression group was shortened(P<0.05), the seizure time was prolonged(P<0.05), and the seizure frequency increased(P<0.05). There was no statistical significance between the empty carrier group and the control group(P>0.05). In animal experiments, compared with the empty vector group and the control group, the apoptosis degree of hippocampal tissue of epileptic mice in the circ_0017178 overexpression group significantly increased(P<0.05), but there was no statistical significance between the empty vector group and the control group(P>0.05). Conclusion Circ_0017178 significantly increases in the expression profile of peripheral blood mononuclear cells in patients with epilepsy, which may act as a "molecular sponge" of miRNA in epilepsy and has the potential of m6A methylation and protein translation. Circ_0017178 may increase the susceptibility and severity of epilepsy by promoting apoptosis in penetetrazole epileptic mice.