MicroRNA-150 contributes to ischemic stroke through its effect on cerebral cortical neuron survival and function by inhibiting ERK1/2 axis via Mal
Authors: Jie Li
Yu-Qin Che
Hui Lv
Journal: Journal of Cellular Physiology (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: ERK1/2 axis; cerebral cortical neurons (CCNs); ischemic stroke; mal; microRNA-150 (miR-150)
Affiliations: Department of Neurology, The Fourth Affiliated Hospital of China Medical University, Shenyang, China.

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. 

Retracted: Yes

PubPeer comments:
 Fig 1 duplication  Fig 2 duplication  Fig 3 resized marker lane  Fig 5 duplications (5D brightness sharpness increased)   , 
 2021 retraction. https: www.atsjournals.org doi full 10.1165 rcmb.v64retraction8 The authors of the March 2015 article by Ghosh and colleagues (1) were notified by the AJRCMB that concerns in the figures in their paper had been identified. Specifically, evidence of duplication was identified in Figures 1, 2A, 3, 5C, and 5D. The senior author (I.B.C.) is deceased and the Journal was informed that he was in sole possession of the original data for the paper. The newly designated corresponding author (A.G.) informed the Journal that the original files could not be accessed; hence, the authors were unable to refute these concerns. They presume that their mishandling of the multi-layered image files and mislabeling of histological sections caused these issues. As these issues undermine confidence in the data, the decision was made to retract the paper. Drs. Ghosh and Chattopadhyay have agreed to this decision (the Journal has been unable to contact or has received no response from Drs. Ganguly, Dey, Banerjee, and Das); they apologize to the Journal and its readers. Reference. Ghosh A, Ganguly S, Dey N, Banerjee S, Das A, Chattopadhyay DJ, Chatterjee IB. Causation of cigarette smokeu2013induced emphysema by p-benzoquinone and its prevention by vitamin C. Am J Respir Cell Mol Biol 2015;52:315u2013322. ,