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MicroRNA-27a-3p Downregulation Inhibits Inflammatory Response and Hippocampal Neuronal Cell Apoptosis by Upregulating Mitogen-Activated Protein Kinase 4 (MAP2K4) Expression in Epilepsy: In Vivo and In Vitro Studies.
Med Sci Monit. 2019 Nov 11; 25:8499-8508.MS

Abstract

BACKGROUND

This study aimed to discover the effect and mechanism of microRNA-27a-3p (miR-27a-3p) in epilepsy. MATERIAL AND

METHODS

To perform our investigation, in vivo and in vitro models of epilepsy were induced using kainic acid (KA). Expression of miR-27a-3p in the hippocampus of epileptic rats or normal rats or neuronal cells was detected using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Racine score was used to assess seizures in epileptic rats. Cell viability and cell apoptosis were analyzed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay and flow cytometry. Enzyme-linked immunosorbent assay (ELISA) was performed to detect inflammatory factors expression.

RESULTS

Significantly higher expression of miR-27a-3p in the hippocampus of epileptic rats and in KA-induced neurons was observed. We found that miR-27a-3p inhibitor alleviated seizures in epileptic rats. miR-27a-3p inhibitor also inhibited apoptosis of hippocampal neurons in epileptic rats, promoted Bcl2 expression, and decreased Bax and Caspase3 expression. The results showed that miR-27a-3p inhibitor effectively reduced the expression levels of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-alpha (TNF-alpha) in hippocampal tissues of epileptic rats. Dual luciferase reporter assay showed that mitogen-activated protein kinase 4 (MAP2K4) was a direct target of miR-27a-3p. miR-27a-3p inhibitor significantly promoted the cell viability of KA-induced neurons, inhibited cell apoptosis, promoted the expression of Bcl-2, and decreased Bax and Caspase3 expression, and all these changes were abolished by MAP2K4-siRNA co-transfection.

CONCLUSIONS

Our preliminary findings indicated that miR-27a-3p inhibitor protected against epilepsy-induced inflammatory response and hippocampal neuronal apoptosis by targeting MAP2K4.

Authors+Show Affiliations

Department of Neurosurgery, The Brain Hospital of Hunan Province, Changsha, Hunan, China (mainland).Department of Neurosurgery, The Brain Hospital of Hunan Province, Changsha, Hunan, China (mainland).Department of Neurosurgery, The Brain Hospital of Hunan Province, Changsha, Hunan, China (mainland).Department of Neurosurgery, The Brain Hospital of Hunan Province, Changsha, Hunan, China (mainland).Department of Neurology, The Central Hospital of Wuhan, Tongji Medical College, Huangzhong University of Science and Technology, Wuhan, Hubei, China (mainland).

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31710596

Citation

Lu, Jun, et al. "MicroRNA-27a-3p Downregulation Inhibits Inflammatory Response and Hippocampal Neuronal Cell Apoptosis By Upregulating Mitogen-Activated Protein Kinase 4 (MAP2K4) Expression in Epilepsy: in Vivo and in Vitro Studies." Medical Science Monitor : International Medical Journal of Experimental and Clinical Research, vol. 25, 2019, pp. 8499-8508.
Lu J, Zhou N, Yang P, et al. MicroRNA-27a-3p Downregulation Inhibits Inflammatory Response and Hippocampal Neuronal Cell Apoptosis by Upregulating Mitogen-Activated Protein Kinase 4 (MAP2K4) Expression in Epilepsy: In Vivo and In Vitro Studies. Med Sci Monit. 2019;25:8499-8508.
Lu, J., Zhou, N., Yang, P., Deng, L., & Liu, G. (2019). MicroRNA-27a-3p Downregulation Inhibits Inflammatory Response and Hippocampal Neuronal Cell Apoptosis by Upregulating Mitogen-Activated Protein Kinase 4 (MAP2K4) Expression in Epilepsy: In Vivo and In Vitro Studies. Medical Science Monitor : International Medical Journal of Experimental and Clinical Research, 25, 8499-8508. https://doi.org/10.12659/MSM.916458
Lu J, et al. MicroRNA-27a-3p Downregulation Inhibits Inflammatory Response and Hippocampal Neuronal Cell Apoptosis By Upregulating Mitogen-Activated Protein Kinase 4 (MAP2K4) Expression in Epilepsy: in Vivo and in Vitro Studies. Med Sci Monit. 2019 Nov 11;25:8499-8508. PubMed PMID: 31710596.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MicroRNA-27a-3p Downregulation Inhibits Inflammatory Response and Hippocampal Neuronal Cell Apoptosis by Upregulating Mitogen-Activated Protein Kinase 4 (MAP2K4) Expression in Epilepsy: In Vivo and In Vitro Studies. AU - Lu,Jun, AU - Zhou,Nina, AU - Yang,Ping, AU - Deng,Lanqiuzi, AU - Liu,Ganzhe, Y1 - 2019/11/11/ PY - 2019/11/12/entrez PY - 2019/11/12/pubmed PY - 2020/3/24/medline SP - 8499 EP - 8508 JF - Medical science monitor : international medical journal of experimental and clinical research JO - Med Sci Monit VL - 25 N2 - BACKGROUND This study aimed to discover the effect and mechanism of microRNA-27a-3p (miR-27a-3p) in epilepsy. MATERIAL AND METHODS To perform our investigation, in vivo and in vitro models of epilepsy were induced using kainic acid (KA). Expression of miR-27a-3p in the hippocampus of epileptic rats or normal rats or neuronal cells was detected using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Racine score was used to assess seizures in epileptic rats. Cell viability and cell apoptosis were analyzed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay and flow cytometry. Enzyme-linked immunosorbent assay (ELISA) was performed to detect inflammatory factors expression. RESULTS Significantly higher expression of miR-27a-3p in the hippocampus of epileptic rats and in KA-induced neurons was observed. We found that miR-27a-3p inhibitor alleviated seizures in epileptic rats. miR-27a-3p inhibitor also inhibited apoptosis of hippocampal neurons in epileptic rats, promoted Bcl2 expression, and decreased Bax and Caspase3 expression. The results showed that miR-27a-3p inhibitor effectively reduced the expression levels of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-alpha (TNF-alpha) in hippocampal tissues of epileptic rats. Dual luciferase reporter assay showed that mitogen-activated protein kinase 4 (MAP2K4) was a direct target of miR-27a-3p. miR-27a-3p inhibitor significantly promoted the cell viability of KA-induced neurons, inhibited cell apoptosis, promoted the expression of Bcl-2, and decreased Bax and Caspase3 expression, and all these changes were abolished by MAP2K4-siRNA co-transfection. CONCLUSIONS Our preliminary findings indicated that miR-27a-3p inhibitor protected against epilepsy-induced inflammatory response and hippocampal neuronal apoptosis by targeting MAP2K4. SN - 1643-3750 UR - https://www.unboundmedicine.com/medline/citation/31710596/MicroRNA_27a_3p_Downregulation_Inhibits_Inflammatory_Response_and_Hippocampal_Neuronal_Cell_Apoptosis_by_Upregulating_Mitogen_Activated_Protein_Kinase_4__MAP2K4__Expression_in_Epilepsy:_In_Vivo_and_In_Vitro_Studies_ L2 - https://www.medscimonit.com/download/index/idArt/916458 DB - PRIME DP - Unbound Medicine ER -