Up-regulated microRNA-199b-3p represses the apoptosis of cerebral microvascular endothelial cells in ischemic stroke through down-regulation of MAPK/ERK/EGR1 axis
Authors: Ming-Yi Hu
Ya-Xiong Yong
Lie-Min Zhou
Hua-Cheng Wang
Ke Han
Hua Yang
Jia Lian
Xiao-Wei Xu
Journal: Cell Cycle (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Ischemic stroke; MAPK/ERK/EGR1axis; cerebral microvascular endothelial cells; microRNA-199b-3p; middle cerebral artery occlusion.
Affiliations: a Guizhou Medical University , Guiyang , P. R. China., b Department of Neurology, the Seventh Affiliated Hospital of Sun Yat-sen University , Shenzhen , P. R. China., c Institute of Medical Sciences, Guizhou Medical University , Guiyang , P.R. China., d Department of Neurosurgery, the Affiliated Hospital of Guizhou Medical University , Guiyang , P. R. China., e Department of Neurology, the Seventh Affiliated Hospital of Sun Yat-sen University , Shenzhen , P.R. China.

Abstract:  MicroRNAs (miRNAs) have emerged as key mediators of posttranscriptional gene silencing in both pathogenic and pathological aspects of ischemic stroke biology. Therefore, the purpose of present study was to explore the effect of microRNA-199b-3p (miR-199b-3p) on the cerebral microvascular endothelial cells (CMECs) in middle cerebral artery occlusion-reperfusion (MCAO-R) mice by regulating MAPK/ERK/EGR1 axis. Mice were used to establish MCAO-R models and to measure the expression of miR-199b-3p and the MAPK/ERK/EGR1 axis-related genes. CMECs were extracted from the MCAO-R mice. A series of mimic or inhibitor for miR-199b-3p, or U0126 (an inhibitor for the MAPK/ERK/EGR1 axis) were introduced to treat these CMECs. The levels of miR-199b-3p and MAPK/ERK/EGR1 axis-related genes in tissues and cells were detected. The effects miR-199b-3p on the process of CMECs, including cell viability, cell cycle and cell apoptosis were evaluated. miR-199b-3p expressed poorly in the brain tissues after MCAO-R, along with activated MAPK/ERK/EGR1 axis and increased CMECs apoptosis. CMECs transfected with miR-199b-3p mimics and U0126 manifested with increased cell viability, more cells arrested at the S stage, and inhibited apoptosis of CMECs. In conclusion, these key results demonstrated up-regulated miR-199b-3p could protect mice against ischemic stroke by inhibiting the apoptosis of CMECs through blockade of MAPK/ERK/EGR1 axis. 

Retracted: Yes

PubPeer comments:
 Fig 6A,  cell cycles in the seven groups . ![file] These cell-cycle analyses make no sense. Each panel contains a wiggly line (raw data histogram), sometimes a smoother line, and red peaks and a hatched hump (G0 G1, G2 M, S components) which are supposed to add up and form the smoother line, but there is no discernable connection between them. , 
 *[below]* Fig 1A B,  the brain tissues of mice in the sham group examined by TTC staining... the TTC staining results of different degrees of neurologic impairment in the MCAOR group . Flipped through 180 deg for easier comparison. *[above]* Fig 2E from [Chang et al (2021)] ,  The cerebral infarction area determined by the TTC method . ![file] A panel appears to be the same, apart from the 2019 version being uncropped and having higher resolution. Could the authors comment? , 
 Retracted [15 July 2022] . ---------------------------- We, the Editors and Publisher of the journal *Cell Cycle*, have retracted the following article: Ya-Xiong Yong, Hua Yang, Jia Lian, Xiao-Wei Xu, Ke Han, Ming-Yi Hu, Hua-Cheng Wang, and LieMin Zhou. Up-regulated microRNA-199b-3p represses the apoptosis of cerebral microvascular endothelial cells in ischemic stroke through down-regulation of MAPK ERK EGR1 axis. Cell Cycle. 2019;18(16):1868u20131881. doi: 10.1080 15384101.2019.1632133 Since publication, concerns have been raised about the integrity of the data in the article. When approached for an explanation, the authors have been unable to address the concerns raised and have not been able to provide their original data. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article. The corresponding author listed in this publication has been informed. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as u2018Retractedu2019. ,