PMID- 38466466 OWN - NLM STAT- MEDLINE DCOM- 20240313 LR - 20240314 IS - 1573-4978 (Electronic) IS - 0301-4851 (Print) IS - 0301-4851 (Linking) VI - 51 IP - 1 DP - 2024 Mar 11 TI - The lncRNA lnc_AABR07044470.1 promotes the mitochondrial-damaged inflammatory response to neuronal injury via miR-214-3p/PERM1 axis in acute ischemic stroke. PG - 412 LID - 10.1007/s11033-024-09301-2 [doi] LID - 412 AB - PURPOSE: We investigated the role of lnc_AABR07044470.1 on the occurrence and development of acute ischemic stroke (AIS) and neuronal injury by targeting the miR-214-3p/PERM1 axis to find a novel clinical drug target and prediction and treatment of AIS. METHODS: The mouse AIS animal model was used in vivo experiments and hypoxia/reoxygenation cell model in vitro was established. Firstly, infarction volume and pathological changes of mouse hippocampal neurons were detected using HE staining. Secondly, rat primary neuron apoptosis was detected by flow cytometry assay. The numbers of neuron, microglia and astrocytes were detected using immunofluorescence (IF). Furthermore, binding detection was performed by bioinformatics database and double luciferase reporter assay. Lnc_AABR07044470.1 localization was performed using fluorescence in situ hybridization (FISH).Lnc_AABR07044470.1, miR-214-3pand PERM1mRNA expression was performed using RT-qPCR. NLRP3, ASC, Caspase-1 and PERM1 protein expression was performed using Western blotting. IL-1beta was detected by ELISA assay. RESULTS: Mouse four-vessel occlusion could easily establish the animal model, and AIS animal model had an obvious time-dependence. HE staining showed that, compared with the sham group, infarction volume and pathological changes of mouse hippocampal neurons were deteriorated in the model group. Furthermore, compared with the sham group, neurons were significantly reduced, while microglia and astrocytes were significantly activated. Moreover, the bioinformatics prediction and detection of double luciferase reporter confirmed the binding site of lnc_AABR07044470.1 to miR-214-3p and miR-214-3p to Perm1. lnc_AABR07044470.1 and PERM1 expression was significantly down-regulated and miR-214-3pexpression was significantly up-regulated in AIS animal model in vivo. At the same time, the expression of inflammasome NLRP3, ASC, Caspase-1 and pro-inflammatory factor IL-1beta was significantly up-regulated in vivo and in vitro. The over-expression of lnc_AABR07044470.1 and miR-214-3p inhibitor could inhibit the neuron apoptosis and the expression of inflammasome NLRP3, ASC, Caspase-1 and pro-inflammatory factor IL-1beta and up-regulate the expression of PERM1 in vitro. Finally, over-expression of lnc_AABR07044470.1 and miR-214-3p inhibitor transfected cell model was significant in relieving the AIS and neuronal injury. CONCLUSION: Lnc_AABR07044470.1 promotes inflammatory response to neuronal injury via miR-214-3p/PERM1 axis in AIS. CI - (c) 2024. The Author(s). FAU - Wang, Meng AU - Wang M AD - First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300380, People's Republic of China. AD - National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, 300380, People's Republic of China. FAU - Li, Hong AU - Li H AD - First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300380, People's Republic of China. AD - National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, 300380, People's Republic of China. FAU - Qian, Yulin AU - Qian Y AD - First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300380, People's Republic of China. AD - National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, 300380, People's Republic of China. FAU - Zhao, Shanshan AU - Zhao S AD - First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300380, People's Republic of China. AD - National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, 300380, People's Republic of China. FAU - Wang, Hao AU - Wang H AD - First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300380, People's Republic of China. AD - National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, 300380, People's Republic of China. FAU - Wang, Yu AU - Wang Y AD - First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300380, People's Republic of China. AD - National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, 300380, People's Republic of China. FAU - Yu, Tao AU - Yu T AD - First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300380, People's Republic of China. nkutongleishi@163.com. AD - National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, 300380, People's Republic of China. nkutongleishi@163.com. LA - eng GR - NO.81704148/the National Natural Science Foundation/ PT - Journal Article DEP - 20240311 PL - Netherlands TA - Mol Biol Rep JT - Molecular biology reports JID - 0403234 RN - 0 (MicroRNAs) RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - 0 (Inflammasomes) RN - 0 (RNA, Long Noncoding) RN - EC 3.4.22.36 (Caspase 1) RN - EC 1.13.12.- (Luciferases) RN - 0 (PERM1 protein, mouse) RN - 0 (Muscle Proteins) RN - 0 (Mirn214 microRNA, rat) SB - IM MH - Rats MH - Mice MH - Animals MH - *MicroRNAs/genetics/metabolism MH - NLR Family, Pyrin Domain-Containing 3 Protein/genetics/metabolism MH - Inflammasomes/metabolism MH - *RNA, Long Noncoding/genetics/metabolism MH - *Ischemic Stroke/genetics/metabolism MH - In Situ Hybridization, Fluorescence MH - Apoptosis MH - Caspase 1/genetics/metabolism MH - Neurons/metabolism MH - Infarction/metabolism/pathology MH - Luciferases/genetics MH - Muscle Proteins/genetics PMC - PMC10927863 OTO - NOTNLM OT - AIS OT - Inflammatory response OT - Lnc_AABR07044470.1 OT - MiR-214-3p OT - Neuronal injury OT - PERM1 COIS- This manuscript has not been published in whole or in part and is not being considered for publication elsewhere. This manuscript does not violate or infringe upon any existing copyright/s license/s from any third party. All authors contributed significantly to work and agree with the manuscript's content. There are no conflicts of interest. EDAT- 2024/03/11 18:42 MHDA- 2024/03/13 06:46 PMCR- 2024/03/11 CRDT- 2024/03/11 12:20 PHST- 2023/08/17 00:00 [received] PHST- 2024/01/30 00:00 [accepted] PHST- 2024/03/13 06:46 [medline] PHST- 2024/03/11 18:42 [pubmed] PHST- 2024/03/11 12:20 [entrez] PHST- 2024/03/11 00:00 [pmc-release] AID - 10.1007/s11033-024-09301-2 [pii] AID - 9301 [pii] AID - 10.1007/s11033-024-09301-2 [doi] PST - epublish SO - Mol Biol Rep. 2024 Mar 11;51(1):412. doi: 10.1007/s11033-024-09301-2.