CEBPA-AS1 Knockdown Alleviates Oxygen-Glucose Deprivation/Reperfusion-Induced Neuron Cell Damage by the MicroRNA 24-3p/BOK Axis

ABSTRACT

Cerebral ischemia/reperfusion (I/R) can lead to serious brain function impairments. Long noncoding RNA (lncRNA) CCAAT enhancer binding protein α antisense RNA 1 (CEBPA-AS1) was shown to be upregulated in human ischemic stroke. This study investigated the function and mechanism of CEBPA-AS1 in I/R. An oxygen-glucose deprivation/reperfusion (OGD/R) model was used to induce I/R injury in SH-SY5Y cells in vitro. RT-qPCR examined the expression of CEBPA-AS1, microRNA 24-3p (miR-24-3p), and Bcl-2-related ovarian killer (Bok). The cell viability, apoptosis, oxidative stress in OGD/R-treated cells were detected using CCK-8, flow cytometry, Western blotting, and enzyme-linked immunosorbent assays. The relationship among genes was tested by RNA pulldown and luciferase reporter assays. We found that OGD/R upregulated CEBPA-AS1 expression in SH-SY5Y cells. Functionally, CEBPA-AS1 depletion ameliorated OGD/R-induced apoptosis and oxidative stress in SH-SY5Y cells by reducing reactive oxygen species production and superoxide dismutase and glutathione. Mechanistic investigations indicated that CEBPA-AS1 acts as a sponge for miR-24-3p, and miR-24-3p binds to BOK. Moreover, miR-24-3p upregulation or BOK downregulation antagonized the protective role of CEBPA-AS1 depletion in SH-SY5Y cells exposed to OGD/R. Overall, downregulation of CEBPA-AS1 exerts protective functions against OGD/R-induced injury by targeting the miR-24-3p/BOK axis.

KEYWORDS:

• CEBPA-AS1
• miR-24-3p
• BOK
• I/R
• OGD/R
• CEBPA-AS1

ACKNOWLEDGMENTS

This study was supported by grants from the National Natural Science Foundation of China (grant 81901343), Suzhou Science and Technology Project (SYS2020067), the Nature Science Research Project of Anhui province (1908085QH356), and the Funding of “Peak” Training Program for Scientific Research of Yijishan Hospital (GF2019G01).

We declare that there are no conflicts of interest regarding the publication of this paper.