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    Epilepsy, one of the most common neurological diseases with spontaneous recurrent seizures, is a severe health problem globally. The present study aimed to study the role and upstream mechanism of 26S proteasome non-ATPase regulatory subunit 11 (Psmd11) in epilepsy. In the current paper, epileptic mice models were successfully established. Hematoxylin and eosin (HE) staining was performed to reveal morphology of hippocampal tissues. Nissl's staining was performed for detection of neuron injury. Enzyme-linked immunosorbent assay (ELISA) was conducted to detect concentrations of pro-inflammatory cytokines. The expression of Psmd11 was downregulated in the hippocampal tissues of epileptic mice, and overexpression of Psmd11 improved the spatial learning and memory of epileptic mice. Further, upregulation of Psmd11 protected epileptic hippocampal neurons from injury. Moreover, Psmd11 overexpression inhibited cell apoptosis, suppressed the activities of microglia and astrocytes, as well as reduced inflammatory response in epileptic hippocampi. Psmd11 was a downstream target of miR-490-3p. Long noncoding RNA (lncRNA) Peg13 bound with miR-490-3p to upregulate Psmd11. Subsequently, rescue experiments revealed that Peg13 suppressed the progression of epilepsy via upregulating Psmd11. Furthermore, Psmd11 was verified to inactivate the Wnt/β-catenin pathway. Peg13 repressed the Wnt/β-catenin pathway via upregulation of Peg13. In conclusion, this paper illuminated the function and upstream mechanism of Psmd11 in epilepsy. Psmd11 was upregulated by Peg13 at a miR-490-3p dependent way, thus inactivating the Wnt/β-catenin pathway and alleviating epilepsy course in mice, which may be a promising approach for epilepsy treatment. AJTR Copyright © 2020.


    Hongxuan Feng, Qian Gui, Wei Zhu, Guanhui Wu, Xiaofeng Dong, Mingqiang Shen, Hailong Luo, Shouru Xue, Qingzhang Cheng. Long-noncoding RNA Peg13 alleviates epilepsy progression in mice via the miR-490-3p/Psmd11 axis to inactivate the Wnt/β-catenin pathway. American journal of translational research. 2020;12(12):7968-7981

    PMID: 33437373

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