Abstract
Previous studies found that miR-374a-5p was decreased in infants suffering from the hypoxic-ischemic encephalopathy (HIE) compared with healthy control infants. However, the molecular mechanism of miR-374a-5p in the development of HIE remained unknown. This study is aimed to investigate the potential molecular pathway for shedding light on the treatment of HIE. An in vitro ischemia model in PC12 cells was established by oxygen/glucose deprivation (OGD). Reverse-transcription quantitative polymerase chain reaction and western blot were used to determine the levels of related genes or proteins in the OGD model or cells obtained from infants with HIE. Flow cytometry was conducted to quantify the apoptosis level of PC12 cells after OGD treatment. The TargetScan prediction algorithm was used to identify the potentially functional targets of miR-374a-5p. A dual-luciferase reporter assay was adopted to elucidate the sequences of miR-374a-5p binding to the 3′-UTR of potential target-PTEN. miR-374a-5p was downregulated in cells derived from human newborns with HIE, rat model with HIE, and PC12 cells after the OGD treatment. Inhibition of miR-374a-5p increased the expression of apoptotic markers and the apoptosis percentage of PC12 cells induced by OGD treatment while overexpression rescued the apoptosis. Meanwhile, PTEN expression was increased and suppressed after miR-374a-5p silence or overexpression, respectively. Upregulation of PTEN reversed the inhibitory effect of apoptotic markers elevation and PC12 cells apoptosis by the overexpression of miR-374a-5p after OGD treatment. PI3K pathway was required for the apoptosis effect caused by PTEN overexpression. We found that overexpression of miR-374a-5p reduced cell apoptosis through inhibiting PTEN/PI3K pathway in PC12 cells treated by OGD.
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Jiang, F., Yang, M., Wu, C. et al. Potential Roles of miR-374a-5p in Mediating Neuroprotective Effects and Related Molecular Mechanism. J Mol Neurosci 69, 123–132 (2019). https://doi.org/10.1007/s12031-019-01340-w
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DOI: https://doi.org/10.1007/s12031-019-01340-w