The MiR-101/EZH2 negative feedback signaling drives oxygen–glucose deprivation/reperfusion-induced injury by activating the MAPK14 signaling pathway in SH-SY5Y cells
Abstract
MiR-101 has been reported to be involved in neuroinflammation, neuronal injury and neurotoxicity. However, the specific role and mechanism of miR-101 in ischemia/reperfusion (I/R)-induced neuronal injury remain largely unknown. Our study found that after oxygen–glucose deprivation/reperfusion (OGD/R) exposure, the level of miR-101 in SH-SY5Y cells was significantly decreased, which was accompanied by a decrease in cell viability, and an increase in LDH release and apoptosis. MiR-101 overexpression (miR-101 mimics) significantly promoted viability and inhibited LDH release and apoptosis in OGD/R-exposed SH-SY5Y cells. Luciferase reporter assay indicated that enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) was a direct target of miR-101, and EZH2 siRNA obviously increased the viability, inhibited LDH release and apoptosis in OGD/R-exposed SH-SY5Y cells. Besides, EZH2 siRNA could inhibit the activation of mitogen-activated protein kinase (MAPK14) signaling pathway and the MAPK14 agonist (anisomycin) could reverse EZH2 siRNA-induced increase in cell viability, and decreases in LDH release and apoptosis. Furthermore, when the methyltransferase activity of EZH2 was inhibited by its specific inhibitor GSK126, the level of miR-101 was increased in OGD/R-exposed SH-SY5Y cells. Additionally, EZH2 siRNA upregulated miR-101 expression in OGD/R-exposed SH-SY5Y cells. Taken together, our findings reveal that miR-101/EZH2 negative feedback signaling drives OGD/R-induced injury by activating the MAPK14 signaling pathway in SH-SY5Y cells.
Copyright (c) 2022 Hao Gu, Qing Chen, Jian Li

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Acta Biochimica Polonica is an open access quarterly and publishes four issues a year. All contents are distributed under the Creative Commons Attribution-ShareAlike 4.0 International (CC BY-SA 4.0) license. Everybody may use the content following terms: Attribution — You must give appropriate credit, provide a link to the license, and indicate if changes were made, ShareAlike — If you remix, transform, or build upon the material, you must distribute your contributions under the same license as the original. There are no additional restrictions — You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.
Copyright for all published papers © stays with the authors.
Copyright for the journal: © Polish Biochemical Society.