PMID- 33014896 OWN - NLM STAT- MEDLINE DCOM- 20210617 LR - 20220531 IS - 2235-2988 (Electronic) IS - 2235-2988 (Linking) VI - 10 DP - 2020 TI - ERG-Associated lncRNA (ERGAL) Promotes the Stability and Integrity of Vascular Endothelial Barrier During Dengue Viral Infection via Interaction With miR-183-5p. PG - 477 LID - 10.3389/fcimb.2020.00477 [doi] LID - 477 AB - Dengue virus (DENV) continues to be a major public health problem. DENV infection will cause mild dengue and severe dengue. Severe dengue is clinically manifested as serious complications, including dengue hemorrhagic fever and/or dengue shock syndrome (DHF/DSS), which is mainly characterized by vascular leakage. Currently, the pathogenesis of severe dengue is not elucidated thoroughly, and there are no known therapeutic targets for controlling the disease effectively. This study aimed to further reveal the potential molecular mechanism of severe dengue. In this study, the long non-coding RNA, ERG-associated lncRNA (lncRNA-ERGAL), was activated and significantly up-regulated in DENV-infected vascular endothelial cells. After knockdown of lncRNA-ERGAL, the expression of ERG, VE-cadherin, and claudin-5 was repressed; besides, cell apoptosis was enhanced, and cytoskeletal remodeling was disordered, leading to instability and increased permeability of vascular endothelial barrier during DENV infection. Fluorescence in situ hybridization (FISH) assay showed lncRNA-ERGAL to be mainly expressed in the cytoplasm. Moreover, the expression of miR-183-5p was found to increase during DENV infection and revealed to regulate ERG, junction-associated proteins, and the cytoskeletal structure after overexpression and knockdown. Then, ERGAL was confirmed to interact with miR-183-5p by luciferase reporter assay. Collectively, ERGAL acted as a miRNA sponge that can promote stability and integrity of vascular endothelial barrier during DENV infection via binding to miR-183-5p, thus revealing the potential molecular mechanism of severe dengue and providing a foundation for a promising clinical target in the future. CI - Copyright (c) 2020 Zheng, Wang, Cui, Guo, Si, Yan, Fang, Jiang, Jiang and Zhou. FAU - Zheng, Baojia AU - Zheng B AD - Department of Microbiology and Immunology, School of Basic Medical Sciences, Jinan University, Guangzhou, China. FAU - Wang, Hui AU - Wang H AD - Department of Microbiology and Immunology, School of Basic Medical Sciences, Jinan University, Guangzhou, China. FAU - Cui, Guohui AU - Cui G AD - Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangzhou, China. AD - Department of Medical Microbiology, Zhongshan Medical College, Sun Yat-sen University, Guangzhou, China. FAU - Guo, Qianfang AU - Guo Q AD - Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangzhou, China. AD - Department of Medical Microbiology, Zhongshan Medical College, Sun Yat-sen University, Guangzhou, China. FAU - Si, Lulu AU - Si L AD - Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangzhou, China. AD - Department of Medical Microbiology, Zhongshan Medical College, Sun Yat-sen University, Guangzhou, China. FAU - Yan, Huijun AU - Yan H AD - Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangzhou, China. AD - Department of Medical Microbiology, Zhongshan Medical College, Sun Yat-sen University, Guangzhou, China. FAU - Fang, Danyun AU - Fang D AD - Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangzhou, China. AD - Department of Medical Microbiology, Zhongshan Medical College, Sun Yat-sen University, Guangzhou, China. FAU - Jiang, Lifang AU - Jiang L AD - Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangzhou, China. AD - Department of Medical Microbiology, Zhongshan Medical College, Sun Yat-sen University, Guangzhou, China. FAU - Jiang, Zhenyou AU - Jiang Z AD - Department of Microbiology and Immunology, School of Basic Medical Sciences, Jinan University, Guangzhou, China. FAU - Zhou, Junmei AU - Zhou J AD - Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangzhou, China. AD - Department of Medical Microbiology, Zhongshan Medical College, Sun Yat-sen University, Guangzhou, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200908 PL - Switzerland TA - Front Cell Infect Microbiol JT - Frontiers in cellular and infection microbiology JID - 101585359 RN - 0 (ERG protein, human) RN - 0 (MIRN183 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (RNA, Long Noncoding) RN - 0 (Transcriptional Regulator ERG) SB - IM MH - *Dengue MH - *Dengue Virus/genetics MH - Endothelial Cells MH - Humans MH - In Situ Hybridization, Fluorescence MH - *MicroRNAs/genetics MH - *RNA, Long Noncoding/genetics MH - Transcriptional Regulator ERG MH - *Virus Diseases PMC - PMC7506072 OTO - NOTNLM OT - ERGAL OT - dengue virus OT - lncRNA OT - miRNA-microRNA OT - permeability OT - severe dengue infection EDAT- 2020/10/06 06:00 MHDA- 2021/06/22 06:00 PMCR- 2020/01/01 CRDT- 2020/10/05 06:21 PHST- 2020/04/05 00:00 [received] PHST- 2020/08/03 00:00 [accepted] PHST- 2020/10/05 06:21 [entrez] PHST- 2020/10/06 06:00 [pubmed] PHST- 2021/06/22 06:00 [medline] PHST- 2020/01/01 00:00 [pmc-release] AID - 10.3389/fcimb.2020.00477 [doi] PST - epublish SO - Front Cell Infect Microbiol. 2020 Sep 8;10:477. doi: 10.3389/fcimb.2020.00477. eCollection 2020.