Krüppel-like factor 4 (KLF4) is a member of the sample Kruppel transcription factor protein family, is an evolutionary conservative contain zinc finger transcription factors, involved in regulating many cellular processes, such as cell growth, proliferation, differentiation and invasion, KLF4 expression in a variety of tissues and cells in the body, has widely in many physiological and pathological conditions. Many studies have shown that KLF4 is involved in neurobiological processes such as neuroinflammation, oxidative stress, apoptosis and axon regeneration, and is closely related to a variety of nervous system diseases such as epilepsy, stroke, and Alzheimer’s disease. Now KLF4 in its role in the development of nervous system diseases were reviewed, help to understand the pathogenesis of the disease and clinical treatment for diseases of the nervous system to provide potential targets.
Objective To study the expression of 4 circular RNA (circRNA) in peripheral blood mononuclear cells (PBMC) of patients with epilepsy and to predict its function by bioinformatics, so as to provide basis for exploring the pathogenesis of epilepsy. Methods From May 2020 to May 2021, 22 epilepsy patients were treated in the Department of Neurology of the First Affiliated Hospital of Baotou Medical College of Inner Mongolia University of Science and Technology, and 22 control group were selected. There were 13 males and 8 females in the epilepsy group, with an average age of (36.41±8.39)years. There were 11 males and 11 females in the control group, with an average age of (34.41±8.68) years. The expression levels of circRNA EFCAB2, C14orf159, PARG and TMEM39 in PBMC were detected by real-time fluorescence quantitative PCR, and their functions were predicted by bioinformatics. Results Compared with the control group, the relative expression of EFCAB2 and C14orf159 in PBMC of epileptic patients was 1.42±0.06 (t=29.41) and 1.31±0.03 (t=25.27), PARG and TMEM39 were not detected in peripheral blood PBMC. Bioinformatics analysis showed that three mirnas obtained by EFCAB2 were miR-6873-3p, miR-6739-3p and miR-7110-3p. Three mirnas were obtained by C14orf159: miR-1180-3p, miR-6501-3p, and miR-3622b-5p. The seizure-related genes were predicted by TargetScan database. EFCAB2: miR-6873-3p met the requirements of 11 downstream genes. A total of 7 downstream genes of miR-6739-3p met the requirements.A total of 14 downstream genes were eligible for miR-7110-3p and a total of 9 downstream genes were eligible for miR-6501-3p. A total of 14 downstream genes were eligible for miR-3622B-5p.miR-1180-3p has a total of 1 downstream genes that meet the requirements. Conclusions Studies have shown that two circrnas, EFCAB2 and C14orf159, may be important biological markers of epilepsy. Through bioinformatics analysis, these two circrnas may act as "molecular sponges" to regulate epilepsy. EFCAB2 has the potential to act as a "molecular sponge" for miR-6873-3p and miR-7110-3p, and it was found that miR-6873-3p and miR-7110-3 share a common downstream target gene MAP1B-which plays a role in epilepsy by regulating voltage-gated sodium channels. C14orf159 can act as a molecular sponge for miR-6501-3p to regulate the expression of CCL3 and play a role in epilepsy.
ObjectiveExplore the mechanism of action of Kruppel-like factor 4 (KLF4) in the oxidative damage model of hippocampal neurons in mice induced by glutamate. MethodsTo clarify the role of KLF4 and glutamate in the oxidative toxicity of epilepsy, the mouse hippocampal neuron cell line (HT22) was adopted, and a neuronal death excitotoxicity cell model was formed by induction with glutamate as the in vitro epilepsy experimental model. The expression level of KLF4 was detected by Real-Time PCR. HT22 cells were transfected with KLF4-specific siRNA, and the experiments were grouped as follows: Ctrl group, Glu group, Glu + siKLF4-1 group, and Glu + siKLF4-2 group. The cell viability of each group was detected by the CCK8 method. ResultsKLF4 was significantly increased in the epilepsy model of HT22 cells induced by glutamate, while downregulation of KLF4 improved the proliferation and viability of neurons in the epilepsy model of HT22 cells induced by glutamate. ConclusionIn the hippocampal neuron cells of epileptic mice, KLF4 is highly expressed. The downregulation of KLF4 improves the proliferation function and vitality of glutamate-induced HT22 cells, indicating that KLF4 may contribute to the occurrence and development of epilepsy by participating in the regulation of oxidative stress responses.