lncRNA AK085865 Promotes Macrophage M2 Polarization in CVB3-Induced VM by Regulating ILF2-ILF3 Complex-Mediated miRNA-192 Biogenesis

Molecular Therapy. Nucleic Acids
Yingying ZhangKun Lv

Abstract

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 effecti...Continue Reading

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Citations

Jan 9, 2021·American Journal of Physiology. Heart and Circulatory Physiology·Yan ZhangMingjie Pang
Apr 4, 2021·International Journal of Molecular Sciences·Peiyu ZhuYuefei Jin

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Datasets Mentioned

BETA
GSE125574
AK085865

Methods Mentioned

BETA
electrophoresis
pull-down
RIP
immunoprecipitation
coimmunoprecipitation
ELISA
fluorescence-activated cell sorter
nuclear translocation
Assay
Feature Extraction

Software Mentioned

GeneSpring
Agilent Feature Extraction
Quantity One Analysis
FlowJo
GraphPad
GraphPad Prism
SPSS

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