PMID- 32668391
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210110
IS  - 2162-2531 (Print)
IS  - 2162-2531 (Electronic)
IS  - 2162-2531 (Linking)
VI  - 21
DP  - 2020 Sep 4
TI  - lncRNA AK085865 Promotes Macrophage M2 Polarization in CVB3-Induced VM by 
      Regulating ILF2-ILF3 Complex-Mediated miRNA-192 Biogenesis.
PG  - 441-451
LID - S2162-2531(20)30178-5 [pii]
LID - 10.1016/j.omtn.2020.06.017 [doi]
AB  - Accumulating evidence indicates that macrophage polarization plays a crucial role 
      in coxsackievirus B3 (CVB3)-induced viral myocarditis (VM). Our previous study 
      demonstrated that long noncoding ribonucleic acid (lncRNA) AK085865 ablation 
      confers susceptibility to VM by regulating macrophage polarization. However, the 
      detailed molecular mechanisms by which AK085865 regulates macrophage polarization 
      remain to be explored. In this study, we found that AK085865 specifically 
      interacts with interleukin enhancer-binding factor 2 (ILF2) and facilitates M2 
      macrophage polarization by functioning as a negative regulator in the ILF2-ILF3 
      complex-mediated microRNA (miRNA or miR) processing pathway. miR-192 was 
      downregulated, whereas the levels of pri-miR-192 were significantly increased in 
      bone marrow-derived macrophages (BMDMs) from AK085865(-/-) mice compared with the 
      BMDMs from wild-type (WT) mice. Conversely, knockdown of ILF2 resulted in 
      elevated levels of mature miR-192 and decreased expression of pri-miR-192 in 
      BMDMs from AK085865(-/-) mice. Moreover, miR-192 overexpression promoted 
      macrophage M2 polarization in vitro, and interleukin-1 receptor-associated kinase 
      1 (IRAK1) was identified as a direct target. miR-192 overexpression effectively 
      rescued mice from lethal myocarditis caused by CVB3 infection and switched 
      myocardial-infiltrating macrophages to a predominant M2 phenotype. Collectively, 
      our findings uncover a critical mechanism of AK085865 in the regulation of 
      macrophage polarization in vitro and in vivo and provide a potential, clinically 
      significant therapeutic target.
CI  - Copyright (c) 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Zhang, Yingying
AU  - Zhang Y
AD  - Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher 
      Education Institutes, Wuhu 241001, China; Department of Laboratory Medicine, The 
      First Affiliated Hospital of Wannan Medical College, Yijishan Hospital, Wuhu 
      241001, China.
FAU - Li, Xueqin
AU  - Li X
AD  - Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher 
      Education Institutes, Wuhu 241001, China; Department of Central Laboratory, The 
      First Affiliated Hospital of Wannan Medical College, Yijishan Hospital, Wuhu 
      241001, China.
FAU - Wang, Chen
AU  - Wang C
AD  - Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's 
      Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, 
      China.
FAU - Zhang, Mengying
AU  - Zhang M
AD  - Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher 
      Education Institutes, Wuhu 241001, China; Department of Central Laboratory, The 
      First Affiliated Hospital of Wannan Medical College, Yijishan Hospital, Wuhu 
      241001, China.
FAU - Yang, Hui
AU  - Yang H
AD  - Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher 
      Education Institutes, Wuhu 241001, China; Department of Central Laboratory, The 
      First Affiliated Hospital of Wannan Medical College, Yijishan Hospital, Wuhu 
      241001, China.
FAU - Lv, Kun
AU  - Lv K
AD  - Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher 
      Education Institutes, Wuhu 241001, China; Department of Central Laboratory, The 
      First Affiliated Hospital of Wannan Medical College, Yijishan Hospital, Wuhu 
      241001, China. Electronic address: lvkun315@126.com.
LA  - eng
PT  - Journal Article
DEP - 20200625
PL  - United States
TA  - Mol Ther Nucleic Acids
JT  - Molecular therapy. Nucleic acids
JID - 101581621
PMC - PMC7358220
OTO - NOTNLM
OT  - IRAK1
OT  - long noncoding RNA
OT  - macrophage polarization
OT  - miR-192
OT  - viral myocarditis
EDAT- 2020/07/16 06:00
MHDA- 2020/07/16 06:01
PMCR- 2020/06/25
CRDT- 2020/07/16 06:00
PHST- 2020/02/26 00:00 [received]
PHST- 2020/04/15 00:00 [revised]
PHST- 2020/06/18 00:00 [accepted]
PHST- 2020/07/16 06:00 [pubmed]
PHST- 2020/07/16 06:01 [medline]
PHST- 2020/07/16 06:00 [entrez]
PHST- 2020/06/25 00:00 [pmc-release]
AID - S2162-2531(20)30178-5 [pii]
AID - 10.1016/j.omtn.2020.06.017 [doi]
PST - ppublish
SO  - Mol Ther Nucleic Acids. 2020 Sep 4;21:441-451. doi: 10.1016/j.omtn.2020.06.017. 
      Epub 2020 Jun 25.