Exosomal miR‐103a‐3p ameliorates lipopolysaccharide‐induced immune response in BEAS‐2B cells via NF‐κB pathway by targeting transducin β‐like 1X related protein 1

Li, Ruina; Liang, Peida; Yuan, Juan; He, Fangzhi

doi:10.1111/1440-1681.13241

Cited by 11 publications

(9 citation statements)

References 40 publications

(78 reference statements)

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“…A recent study also reported that miR-103a-3p was upregulated in EVs during ZIKV infection ( Tabari et al, 2020 ). MiR-103a-3p has multiple functions involved in the regulation of inflammation, immune response, and development of a variety of cancers ( Geng et al, 2014 ; Hu et al, 2018 ; Lu et al, 2019 ; Li et al, 2020 , 2021 ). However, to date, the effect of miR-103a-3p on the regulation of pathogen infection has not been reported.…”

Section: Discussionmentioning

confidence: 99%

MiR-103a-3p Promotes Zika Virus Replication by Targeting OTU Deubiquitinase 4 to Activate p38 Mitogen-Activated Protein Kinase Signaling Pathway

et al. 2022

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BackgroundMicroRNAs (miRNAs) play critical roles in regulating virus infection and replication. However, the mechanism by which miRNA regulates Zika virus (ZIKV) replication remains elusive. We aim to explore how the differentially expressed miR-103a-3p regulates ZIKV replication and to clarify the underlying molecular mechanism.MethodsSmall RNA sequencing (RNA-Seq) was performed to identify differentially expressed miRNAs in A549 cells with or without ZIKV infection and some of the dysregulated miRNAs were validated by quantitative real time PCR (qRT-PCR). The effect of miR-103a-3p on ZIKV replication was examined by transfecting miR-103a-3p mimic or negative control (NC) into A549 cells with or without p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 and expression levels of ZIKV NS5 mRNA and NS1 protein were detected by qRT-PCR and Western blot, respectively. The potential target genes for miR-103a-3p were predicted by four algorithms and further validated by mutation analysis through luciferase reporter assay. The predicated target gene OTU deubiquitinase (DUB) 4 (OTUD4) was over-expressed by plasmid transfection or silenced by siRNA transfection into cells prior to ZIKV infection. Activation status of p38 MAPK signaling pathway was revealed by looking at the phosphorylation levels of p38 (p-p38) and HSP27 (p-HSP27) by Western blot.ResultsThirty-five differentially expressed miRNAs in ZIKV-infected A549 cells were identified by RNA-Seq analysis. Five upregulated and five downregulated miRNAs were further validated by qRT-PCR. One of the validated upregulated miRNAs, miR-103a-3p significantly stimulated ZIKV replication both at mRNA (NS5) and protein (NS1) levels. We found p38 MAPK signaling was activated following ZIKV infection, as demonstrated by the increased expression of the phosphorylation of p38 MAPK and HSP27. Blocking p38 MAPK signaling pathway using SB203580 inhibited ZIKV replication and attenuated the stimulating effect of miR-103a-3p on ZIKV replication. We further identified OTUD4 as a direct target gene of miR-103a-3p. MiR-103a-3p over-expression or OTUD4 silencing activated p38 MAPK signaling and enhanced ZIKV replication. In contrast, OTUD4 over-expression inhibited p38 MAPK activation and decreased ZIKV replication. In addition, OTUD4 over-expression attenuated the stimulating effect of miR-103a-3p on ZIKV replication and activation of p38 MAPK signaling.ConclusionZika virus infection induced the expression of miR-103a-3p, which subsequently activated p38 MAPK signaling pathway by targeting OTUD4 to facilitate ZIKV replication.

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Section: Discussionmentioning

confidence: 99%

MiR-103a-3p Promotes Zika Virus Replication by Targeting OTU Deubiquitinase 4 to Activate p38 Mitogen-Activated Protein Kinase Signaling Pathway

et al. 2022

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“…miRNAs including miR-124, miR-146a, and miR-181b-5p are critical for regulating microglial development and activation. [ 36 – 38 ] miR-103a-3p is linked with cancer progression [ 39 – 41 ] but also performs a variety of physiological functions across multiple biological processes, including immunity [ 42 ] and oxidative stress. [ 43 ] miR-103a-3p is significantly downregulated in LPS-treated lung cells; miR-103a-3p overexpression reduces LPS-induced inflammation, [ 42 , 44 ] showing a protective effect of these non-coding RNA molecules against inflammation.…”

Section: Discussionmentioning

confidence: 99%

“…[ 36 – 38 ] miR-103a-3p is linked with cancer progression [ 39 – 41 ] but also performs a variety of physiological functions across multiple biological processes, including immunity [ 42 ] and oxidative stress. [ 43 ] miR-103a-3p is significantly downregulated in LPS-treated lung cells; miR-103a-3p overexpression reduces LPS-induced inflammation, [ 42 , 44 ] showing a protective effect of these non-coding RNA molecules against inflammation. [ 43 ] The contribution of miR-103a-3p to neurological diseases, however, has rarely been reported.…”

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine Mitigates Microglial Activation Associated with Postoperative Cognitive Dysfunction by Modulating the MicroRNA-103a-3p/VAMP1 Axis

Wang

Shi

et al. 2022

Neural Plasticity

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Surgery-induced microglial activation is critical in mediating postoperative cognitive dysfunction (POCD) in elderly patients, where the important protective effect of dexmedetomidine has been indicated. However, the mechanisms of action of dexmedetomidine during the neuroinflammatory response that underlies POCD remain largely unknown. We found that lipopolysaccharide (LPS) induced substantial inflammatory responses in primary and BV2 microglial cells. The screening of differentially expressed miRNAs revealed that miR-103a-3p was downregulated in these cell culture models. Overexpression of miR-103a-3p mimics and inhibitors suppressed and enhanced the release of inflammatory factors, respectively. VAMP1 expression was upregulated in LPS-treated primary and BV-2 microglial cells, and it was validated as a downstream target of miR-103-3p. VAMP1-knockdown significantly inhibited the LPS-induced inflammatory response. Dexmedetomidine treatment markedly inhibited LPS-induced inflammation and the expression of VAMP1, and miR-103a-3p expression reversed this inhibition. Moreover, dexmedetomidine mitigated microglial activation and the associated inflammatory response in a rat model of surgical trauma that mimicked POCD. In this model, dexmedetomidine reversed miR-103a-3p and VAMP1 expression; this effect was abolished by miR-103a-3p overexpression. Taken together, the data show that miR-103a-3p/VAMP1 is critical for surgery-induced microglial activation of POCD.

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“…Overexpression of exosomal miR-103a-3p attenuates inflammation by regulating immune response via transducing β-like 1X related protein 1/NF-κB signaling pathway. 559 …”

Section: The Roles Of Exosomal Ncrnas In Human Diseasesmentioning

confidence: 99%

Roles and mechanisms of exosomal non-coding RNAs in human health and diseases

et al. 2021

Sig Transduct Target Ther

220

127

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Exosomes play a role as mediators of cell-to-cell communication, thus exhibiting pleiotropic activities to homeostasis regulation. Exosomal non-coding RNAs (ncRNAs), mainly microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are closely related to a variety of biological and functional aspects of human health. When the exosomal ncRNAs undergo tissue-specific changes due to diverse internal or external disorders, they can cause tissue dysfunction, aging, and diseases. In this review, we comprehensively discuss the underlying regulatory mechanisms of exosomes in human diseases. In addition, we explore the current knowledge on the roles of exosomal miRNAs, lncRNAs, and circRNAs in human health and diseases, including cancers, metabolic diseases, neurodegenerative diseases, cardiovascular diseases, autoimmune diseases, and infectious diseases, to determine their potential implication in biomarker identification and therapeutic exploration.

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Exosomal miR‐103a‐3p ameliorates lipopolysaccharide‐induced immune response in BEAS‐2B cells via NF‐κB pathway by targeting transducin β‐like 1X related protein 1

Cited by 11 publications

References 40 publications

MiR-103a-3p Promotes Zika Virus Replication by Targeting OTU Deubiquitinase 4 to Activate p38 Mitogen-Activated Protein Kinase Signaling Pathway

MiR-103a-3p Promotes Zika Virus Replication by Targeting OTU Deubiquitinase 4 to Activate p38 Mitogen-Activated Protein Kinase Signaling Pathway

Dexmedetomidine Mitigates Microglial Activation Associated with Postoperative Cognitive Dysfunction by Modulating the MicroRNA-103a-3p/VAMP1 Axis

Roles and mechanisms of exosomal non-coding RNAs in human health and diseases

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