Retracted: MicroRNA‐150 contributes to ischemic stroke through its effect on cerebral cortical neuron survival and function by inhibiting ERK1/2 axis via Mal

Abstract

Ischemic stroke, caused by the blockage of blood supply, is a major cause of death worldwide. For identifying potential candidates, we explored the effects microRNA-150 (miR-150) has on ischemic stroke and its underlying mechanism by developing a stable middle cerebral artery occlusion (MCAO) rat model. Gene expression microarray analysis was performed to screen differentially expressed genes associated with MCAO. We evaluated the expression of miR-150 and Mal and the status of ERK1/2 axis in the brain tissues of MCAO rats. Then the cerebral cortical neurons (CCNs) were obtained and introduced with elevated or suppressed miR-150 or silenced Mal to validate regulatory mechanisms for miR-150 governing Mal in vitro. The relationship between miR-150 and Mal was verified by dual luciferase reporter gene assay. Besides, cell growth and apoptosis of CCNs were detected by means of MTT assay and flow cytometry analyses. We identified Mal as a downregulated gene in MCAO, based on the microarray data of GSE16561. MiR-150 was over-expressed and negatively targeted Mal in the brain tissues obtained from MCAO rats and their CCNs. Increasing miR-150 blocked the ERK1/2 axis, resulting in an inhibited cell growth of CNNs but an enhanced apoptosis. Furthermore, MiR-150 inhibition was observed to have effects on CNNs as opposed to those inhibited by miR-150 promotion. The key findings of this study support the notion that miR-150 under-expression-mediated direct promotion of Mal protects CNN functions through the activation of the ERK1/2 axis, and underscore the concept that miR-150 may represent a novel pharmacological target for ischemic stroke intervention.

Promotive role of microRNA‑150 in hippocampal neurons apoptosis in vascular dementia model rats

“…Since ligustrazine is considered as a neuroprotective agent in the management of Vd disease by suppressing Pc12 cell apoptosis (32), it was also hypothesized that mir-150 knockdown might protect against Vd by inhibiting Pc12 cell apoptosis. a previous study demonstrated that mir-150 knockdown functions in the survival of cerebral cortical neurons (33). in the present study, compared with the empty vector group, HoXa1 overexpression significantly inhibited mir-150 mimic-induced Pc12 cell apoptosis, which suggested that mir-150 might mediate the biological function of Pc12 cells via HoXa1.…”

miR-124 Alleviates Ischemic Stroke-Induced Neuronal Death by Targeting DAPK1 in Mice

“…miRNAs participate in the posttranscriptional regulation of gene expression and are involved in neurogenesis, development, and maintenance of neuronal phenotype (Kaur et al, 2013;Yapijakis, 2020). miRNA-dependent regulation of neuronal survival and ischemic stroke is a research topic of growing interest (Guo et al, 2017;Lv et al, 2019;Wu F. et al, 2019). Several studies have reported that a considerable number of miRNAs are altered following focal cerebral ischemia, some of which have been implicated in the modulation of inflammation (Jaenisch et al, 2016), autophagy (Zhao et al, 2017), apoptosis (Zhang and Meng, 2019), and oxidative stress (Kanagaraj et al, 2014) by regulating target protein levels.…”

Study on Neuroprotective Mechanism of Houshiheisan in Ischemic Stroke Based on Transcriptomics and Experimental Verification

“…Upregulating ERK1/2 pathway activity is associated with neuronal survival in ischemic stroke models in vivo and in vitro [ 37 , 38 ]. ERK1/2 acts as a neuroprotective agent by inhibiting postischemic oxidative stress and mitochondria-dependent apoptosis of neural cells [ 39 , 40 ]. ERK1/2 activation can promote the phosphorylation of CREB, increase the expression of prosurvival protein Bcl-2, inhibit ischemia-induced neuronal apoptosis, and enhance neuronal survival [ 41 , 42 ].…”