PMID- 30419554 OWN - NLM STAT- MEDLINE DCOM- 20181211 LR - 20190212 IS - 1421-9778 (Electronic) IS - 1015-8987 (Linking) VI - 50 IP - 6 DP - 2018 TI - MALAT1 Activates the P53 Signaling Pathway by Regulating MDM2 to Promote Ischemic Stroke. PG - 2216-2228 LID - 10.1159/000495083 [doi] AB - BACKGROUND/AIMS: This study focused on evaluating the effect of MALAT1 and MDM2 on ischemic stroke through regulation of the p53 signaling pathway. MATERIALS: Bioinformatics analysis was performed to identify abnormally expressed lncRNAs, mRNAs and their associated pathways. Oxygen-glucose deprivation/reoxygenation (OGD/R) in cells and middle cerebral artery occlusion/reperfusion (MCAO/R) in mice were performed to simulate an ischemic stroke environment. Western blot and qRT-PCR were used to examine lncRNA expression and mRNA levels. Fluorescence in situ hybridization (FISH) LncRNA was used to locate mRNA. MTT and flow cytometry were performed to examine cell proliferation and apoptosis. Finally, immunohistochemistry was used to observe the expression of genes in vivo. RESULTS: MALAT1 and MDM2, which exhibit strong expression in stroke tissues, were subjected to bioinformatics analysis, and the p53 pathway was chosen for further study. MALAT1, MDM2 and p53 signaling pathway-related proteins were all up regulated in OGD/R cells. Furthermore, Malat1, Mdm2 and p53 pathway related-proteins were also up regulated in MCAO/R mice. Both MALAT1 and MDM2 were localized in the nuclei. Down regulation of MALAT1 and MDM2 enhanced cell proliferation ability and reduced apoptosis, resulting in decreased infarct size in MCAO/R brains. CONCLUSION: These results indicate that MALAT1/MDM2/p53 signaling pathway axis may provide more effective clinical therapeutic strategy for patients with ischemic stroke. CI - (c) 2018 The Author(s). Published by S. Karger AG, Basel. FAU - Zhang, Ting AU - Zhang T AD - Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China549832649@qq.com. FAU - Wang, Hongmei AU - Wang H AD - Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. FAU - Li, Qiang AU - Li Q AD - Department of Neurology, Shanghai Jiao Tong University Affillilated Ninth People's Hospital, Shanghai, China. FAU - Fu, Jianliang AU - Fu J AD - Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. FAU - Huang, Jiankang AU - Huang J AD - Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. FAU - Zhao, Yuwu AU - Zhao Y AD - Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. LA - eng PT - Journal Article DEP - 20181112 PL - Germany TA - Cell Physiol Biochem JT - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology JID - 9113221 RN - 0 (MALAT1 long non-coding RNA, human) RN - 0 (RNA, Long Noncoding) RN - 0 (RNA, Small Interfering) RN - 0 (Tumor Suppressor Protein p53) RN - 0 (bcl-2-Associated X Protein) RN - EC 2.3.2.27 (Proto-Oncogene Proteins c-mdm2) RN - IY9XDZ35W2 (Glucose) RN - S88TT14065 (Oxygen) SB - IM MH - Animals MH - Brain/metabolism/pathology MH - Cell Hypoxia MH - Cell Proliferation MH - Endothelial Cells/cytology/metabolism MH - Glucose/deficiency MH - Humans MH - Infarction, Middle Cerebral Artery/complications/pathology MH - Mice MH - Oxygen/metabolism MH - Proto-Oncogene Proteins c-mdm2/antagonists & inhibitors/genetics/*metabolism MH - RNA Interference MH - RNA, Long Noncoding/antagonists & inhibitors/genetics/*metabolism MH - RNA, Small Interfering/metabolism MH - Signal Transduction MH - Stroke/etiology/metabolism/pathology MH - Tumor Suppressor Protein p53/antagonists & inhibitors/genetics/*metabolism MH - bcl-2-Associated X Protein/metabolism OTO - NOTNLM OT - Ischemic stroke OT - MALAT1 OT - MDM2 OT - P53 pathway EDAT- 2018/11/13 06:00 MHDA- 2018/12/12 06:00 CRDT- 2018/11/13 06:00 PHST- 2018/07/10 00:00 [received] PHST- 2018/11/05 00:00 [accepted] PHST- 2018/11/13 06:00 [pubmed] PHST- 2018/12/12 06:00 [medline] PHST- 2018/11/13 06:00 [entrez] AID - 000495083 [pii] AID - 10.1159/000495083 [doi] PST - ppublish SO - Cell Physiol Biochem. 2018;50(6):2216-2228. doi: 10.1159/000495083. Epub 2018 Nov 12.