PMID- 30496821 OWN - NLM STAT- MEDLINE DCOM- 20190307 LR - 20190307 IS - 1873-7544 (Electronic) IS - 0306-4522 (Linking) VI - 397 DP - 2019 Jan 15 TI - MALAT1 lncRNA Induces Autophagy and Protects Brain Microvascular Endothelial Cells Against Oxygen-Glucose Deprivation by Binding to miR-200c-3p and Upregulating SIRT1 Expression. PG - 116-126 LID - S0306-4522(18)30757-7 [pii] LID - 10.1016/j.neuroscience.2018.11.024 [doi] AB - There is growing evidence that long noncoding RNAs (lncRNAs) play important roles in various biological processes. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is one of the most highly upregulated lncRNAs in cerebral ischemia. However, the molecular mechanism of MALAT1 during cerebral ischemia is still unclear. This experiment is intended to investigate the role of MALAT1 in cerebral ischemia and its relationship with autophagy. Oxygen-glucose deprivation (OGD) in brain microvascular endothelial cells (BMECs) was used to mimic ischemic-like conditions in vitro. Real-time PCR, MTT, LDH assay and western blot were used to evaluate the levels of MALAT1, miR-200c-3p, SIRT1, cell survival and proteins. We found that the expression of MALAT1 and LC3BII were upregulated and p62 was downregulated by OGD. Inhibition of MALAT1 attenuated the autophagy activation and promoted cell death. We further revealed that MALAT1 downregulated the expression of miR-200c-3p by directly binding to miR-200c-3p. Furthermore, miR-200c-3p inhibited the autophagy and survival in BMECs by binding to 3'UTR of SIRT1, whereas MALAT1 overturned the inhibitory effect of miR-200c-3p. In conclusion, our study illuminated a novel Malat1-miR-200c-3p-SIRT1 pathway in the regulation of autophagy, in which, MALAT1 activates autophagy and promotes cell survival by binding to miR-200c-3p and upregulating SIRT1 expression. CI - Copyright (c) 2018 IBRO. Published by Elsevier Ltd. All rights reserved. FAU - Wang, Shan AU - Wang S AD - Department of Anesthesiology, Second Affiliated Hospital of Harbin Medical University, Harbin, China. FAU - Han, Xu AU - Han X AD - Department of Anesthesiology, Second Affiliated Hospital of Harbin Medical University, Harbin, China. FAU - Mao, Zhengchun AU - Mao Z AD - Department of Anesthesiology, Second Affiliated Hospital of Harbin Medical University, Harbin, China. FAU - Xin, Yanming AU - Xin Y AD - Department of Anesthesiology, Second Affiliated Hospital of Harbin Medical University, Harbin, China. FAU - Maharjan, Surendra AU - Maharjan S AD - Department of Anesthesiology, Second Affiliated Hospital of Harbin Medical University, Harbin, China. FAU - Zhang, Bing AU - Zhang B AD - Department of Anesthesiology, Second Affiliated Hospital of Harbin Medical University, Harbin, China. Electronic address: zhang_bing08@126.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20181126 PL - United States TA - Neuroscience JT - Neuroscience JID - 7605074 RN - 0 (Malat1 long non-coding RNA, mouse) RN - 0 (MicroRNAs) RN - 0 (Mirn200 microRNA, mouse) RN - 0 (RNA, Long Noncoding) RN - EC 3.5.1.- (Sirt1 protein, mouse) RN - EC 3.5.1.- (Sirtuin 1) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Animals MH - Autophagy/*physiology MH - Brain/blood supply/*metabolism MH - Cell Hypoxia/*physiology MH - Cell Line MH - Cell Survival/physiology MH - Endothelial Cells/*metabolism MH - Glucose/*deficiency MH - Mice MH - MicroRNAs/metabolism MH - Microvessels/metabolism MH - RNA, Long Noncoding/*metabolism MH - Sirtuin 1/metabolism MH - Up-Regulation OTO - NOTNLM OT - BMECs OT - MALAT1 OT - MiR-200c-3p OT - SIRT1 OT - autophagy OT - lncRNA EDAT- 2018/11/30 06:00 MHDA- 2019/03/08 06:00 CRDT- 2018/11/30 06:00 PHST- 2018/09/15 00:00 [received] PHST- 2018/11/11 00:00 [revised] PHST- 2018/11/15 00:00 [accepted] PHST- 2018/11/30 06:00 [pubmed] PHST- 2019/03/08 06:00 [medline] PHST- 2018/11/30 06:00 [entrez] AID - S0306-4522(18)30757-7 [pii] AID - 10.1016/j.neuroscience.2018.11.024 [doi] PST - ppublish SO - Neuroscience. 2019 Jan 15;397:116-126. doi: 10.1016/j.neuroscience.2018.11.024. Epub 2018 Nov 26.