Research Paper Volume 13, Issue 18 pp 22242—22255
miR-21 regulates ischemic neuronal injury via the p53/Bcl-2/Bax signaling pathway
- 1 Department of Pathology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, P.R. China
Received: January 21, 2021 Accepted: September 3, 2021 Published: September 22, 2021
https://doi.org/10.18632/aging.203530How to Cite
Copyright: © 2021 Yan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Focal cerebral ischemia leads to a large number of neuronal apoptosis, and secondary neuronal death is the main cause of cerebral infarction. MicroRNA-21 (miR-21) has been shown to be a strong anti-apoptosis and pro-survival factor in ischemia. However, the precise mechanism of miR-21 in ischemic neuroprotection remains largely unknown. In this study, miR-21 was down-regulated while p53 was up-regulated following ischemia in vitro and in vivo. Overexpression of miR-21 in vitro and in vivo substantially inhibited the expression of p53 following ischemia, while inhibition of miR-21 in vitro and in vivo promoted p53 expression following ischemia. Moreover, the miR-21/p53 axis regulated the expression of Bcl-2/Bax and abolished OGD/R-induced neuronal injury in vitro. Furthermore, overexpression of miR-21 in vivo reduced neuronal death, protected against ischemic damage, and improved neurological functions by inhibiting p53/Bcl-2/Bax signaling, while inhibition of miR-21 enhanced the p53/Bcl-2/Bax signaling and aggravated the ischemic neuronal injury in vivo. Our data uncover a novel mechanism of miR-21 in regulating cerebral ischemic neuronal injury by inhibiting p53/Bcl-2/Bax signaling pathway, which suggests that miR-21/p53 may be attractive therapeutic molecules for treatment of ischemic stroke.
Abbreviations
miRNAs: microRNAs; I/R: ischemia/reperfusion; miR-21: miRNA-21; OGD/R: oxygen-glucose deprivation and reoxygenation; ncRNAs: non-coding RNAs; qRT-PCR: quantitative reverse transcription-polymerase chain reaction; siRNA: small interfering RNA; p53-siRNA: siRNA targeting p53; p53-s-siRNA: scramble RNA for p53-siRNA; PI: propidium iodide; MCAO: middle cerebral artery occlusion; TTC: 2,3,5-Triphenyltetrazolium chloride; p53-DBD: p53 DNA Binding Domain; FRET: Förster resonance energy transfer; PDL: poly D-lysine.