<scp>lncRNA MEG3</scp> restrained the <scp>M1</scp> polarization of microglia in acute spinal cord injury through the <scp>HuR</scp>/<scp>A20</scp>/<scp>NF‐κB</scp> axis

Zhou, Haibin; Wang, Liqing; Zhan, Renya; Zheng, Xianliang; Zheng, Junbao

doi:10.1111/bpa.13070

Cited by 9 publications

(5 citation statements)

References 51 publications

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“…35 Through bioinformatic analysis in this study, nine RBPs were identified with a high probability of binding to MEG3. Since lncRNA MEG3 has been demonstrated to regulate microglial M1 polarization by binding to HuR, 37 It has been reported that HuR primarily works at the post-transcriptional level, which can enhance the translation and/ or mRNA stability of its target genes. 53 CCL5 plays a fundamental role in inflammation by recruiting leukocytes to inflammatory sites.…”

Section: Discussionmentioning

confidence: 99%

“…The results show that HuR was enriched in the Bio-MEG3 sense group relative to that in the Bio-MEG3 antisense group (Figure 4B), suggesting that MEG3 strongly binds to HuR in M1-and M2-polarized HuR Downregulates CCL5 by Inhibiting CCL5 Transcription in M1 and M2 Macrophages lncRNAs have been shown to maintain mRNA stability by recruiting RBPs at the post-transcriptional level. 37 HuRrepressed CCL5 transcription in breast cancer cells is mediated by an interferon-stimulated response element in the CCL5 promoter. 40 Based on these findings, we hypothesized that MEG3 regulates CCL5 expression by interacting with HuR.…”

Section: Lncrna Meg3 Binds To Hur In M1-and M2-like Macrophagesmentioning

confidence: 97%

“…ELAVL1/HuR is a ubiquitous RBP that can enhance mRNA stability and thus induce the expression of numerous lncRNAs, 44 and can be regulated by lncRNA MEG3 in BV2 cells. 37 An RNA pull-down assay was performed to detect the possible relationship between MEG3 and HuR. The results show that HuR was enriched in the Bio-MEG3 sense group relative to that in the Bio-MEG3 antisense group (Figure 4B), suggesting that MEG3 strongly binds to HuR in M1-and M2-polarized HuR Downregulates CCL5 by Inhibiting CCL5 Transcription in M1 and M2 Macrophages lncRNAs have been shown to maintain mRNA stability by recruiting RBPs at the post-transcriptional level.…”

Section: Lncrna Meg3 Binds To Hur In M1-and M2-like Macrophagesmentioning

confidence: 99%

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LncRNA MEG3 Reduces the Ratio of M2/M1 Macrophages Through the HuR/CCL5 Axis in Hepatocellular Carcinoma

Wei,

Wu,

Huang

et al. 2024

JHC

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Tumor-associated macrophages play a crucial role in the development of hepatocellular carcinoma (HCC). Our study aimed to investigate the relationship between long coding RNA (lncRNA) maternally expressed gene 3 (MEG3), RNA-binding protein human antigen R (HuR), and messenger RNA C-C motif chemokine 5 (CCL5) in the modulation of M1 and M2 macrophage polarization in HCC. Methods: To induce M1 or M2 polarization, LPS/IFNγ-or IL4/IL13 were used to treat bone marrow derived macrophages (BMDMs). The localization of MEG3 in M1 and M2 macrophages was assessed using fluorescence in situ hybridization assay. Expression levels of MEG3, HuR, CCL5, M1, and M2 markers were measured by RT-qPCR or immunofluorescence staining. Flow cytometry was performed to determine the proportion of F4/80+CD206+ and F4/80+CD68+ cells. RNA pulldown assay was performed to detect the binding of lncRNA MEG3 and HuR. The impacts of HuR on CCL5 stability and activity of CCL5 promoter were evaluated using actinomycin D treatment and luciferase reporter assay. Cell migration, invasiveness, and angiogenesis were assessed using transwell migration and invasion assays and a tube formation assay. A mixture of Huh-7 cells and macrophages were injected into nude mice to explore the effect of MEG3 on tumorigenesis. Results: MEG3 promoted M1-like polarization while dampening M2-like polarization of BMDMs. MEG3 bound to HuR in M1 and M2 macrophages. HuR downregulated CCL5 by inhibiting CCL5 transcription in macrophages. In addition, overexpression of MEG3 suppressed cell metastasis, invasion, and angiogenesis by obstructing macrophage M2 polarization. MEG3 inhibited tumorigenesis in HCC via promotion of M1-like polarization and inhibition of M2-like polarization. Rescue experiments showed that depletion of CCL5 in M2 macrophages reversed MEG3-induced suppressive effect on cell migration, invasion, and tube formation. Conclusion: MEG3 suppresses HCC progression by promoting M1-like while inhibiting M2-like macrophage polarization via binding to HuR and thus upregulating CCL5.

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Section: Discussionmentioning

confidence: 99%

Section: Lncrna Meg3 Binds To Hur In M1-and M2-like Macrophagesmentioning

confidence: 97%

Section: Lncrna Meg3 Binds To Hur In M1-and M2-like Macrophagesmentioning

confidence: 99%

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LncRNA MEG3 Reduces the Ratio of M2/M1 Macrophages Through the HuR/CCL5 Axis in Hepatocellular Carcinoma

Wei,

Wu,

Huang

et al. 2024

JHC

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“…Although the role of EA in neurological recovery after SCI is known, its underlying mechanism remains unknown. Growing evidence has pointed to the notion that HuR, a RNA binding protein, play a pivotal role in nerve regeneration, apoptosis, and various diseases related to the central nervous system (Sorge et al, 2022;Zhou et al, 2022a). Kwan, Thaddaeus's study shows that HuR is translocated from the nucleus to the cytoplasm in the acute phase of SCI, further accentuating neuronal injury (Kwan et al, 2017b).…”

Section: Discussionmentioning

confidence: 99%

Electroacupuncture Relieves HuR/KLF9-Mediated Inflammation to Enhance Neurological Repair after Spinal Cord Injury

Zhang,

Xu,

et al. 2023

eNeuro

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Electroacupuncture (EA) is widely applied in clinical therapy for spinal cord injury (SCI). However, the associated molecular mechanism has yet to be elucidated. The current study aimed to investigate the underlying mechanism of EA in neurologic repair after SCI. First, we investigated the role of EA in the neurologic repair of the SCI rat model. The expression levels of human antigen R (HuR) and Krüppel-like factor 9 (KLF9) in spinal cord tissues were quantified after treatment. Second, we conducted bioinformatics analysis, RNA pull-down assays, RNA immunoprecipitation, and luciferase reporter gene assay to verify the binding of HuR and KLF9 mRNA for mRNA stability. Last, HuR inhibitor CMLD-2 was used to verify the enhanced effect of EA on neurologic repair after SCI via the HuR/KLF9 axis. Our data provided convincing evidence that EA facilitated the recovery of neuronal function in SCI rats by reducing apoptosis and inflammation of neurons. We found that EA significantly diminished the SCI-mediated upregulation of HuR, and HuR could bind to the 3′ untranslated region of KLF9 mRNA to protect its decay. In addition, a series ofin vivoexperiments confirmed that CMLD-2 administration increased EA-mediated pain thresholds and motor function in SCI rats. Collectively, the present study showed that EA improved pain thresholds and motor function in SCI rats via impairment of HuR-mediated KLF9 mRNA stabilization, thus providing a better understanding of the regulatory mechanisms regarding EA-mediated neurologic repair after SCI.

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“…In the same study, miR‐29 was shown to function as a decoy and prevent HuR‐mediated degradation of A20 . Recently, the lncRNA, MEG3 , which is suppressed in acute SCI was found to bind to HuR in microglial cells and promote its ubiquitination degradation resulting in an upregulation of A20 and suppression of M1‐like polarization (Zhou et al, 2022). Inhibition of HuR via the ectopic expression of MEG3 suppressed M1 polarization and improved motor function after SCI.…”

Section: Cns Disorders Where Are‐mediated Rna Regulation Has Been Inv...mentioning

confidence: 99%

RNA regulation of inflammatory responses in glia and its potential as a therapeutic target in central nervous system disorders

Guha

Husain

et al. 2022

Glia

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A major hallmark of neuroinflammation is the activation of microglia and astrocytes with the induction of inflammatory mediators such as IL-1β, TNF-α, iNOS, and IL-6.Neuroinflammation contributes to disease progression in a plethora of neurological disorders ranging from acute CNS trauma to chronic neurodegenerative disease.Posttranscriptional pathways of mRNA stability and translational efficiency are major drivers for the expression of these inflammatory mediators. A common element in this level of regulation centers around the adenine-and uridine-rich element (ARE) which is present in the 3 0 untranslated region (UTR) of the mRNAs encoding these inflammatory mediators. (ARE)-binding proteins (AUBPs) such as Human antigen R (HuR), Tristetraprolin (TTP) and KH-type splicing regulatory protein (KSRP) are key nodes for directing these posttranscriptional pathways and either promote (HuR) or suppress (TTP and KSRP) glial production of inflammatory mediators. This review will discuss basic concepts of ARE-mediated RNA regulation and its impact on glial-driven neuroinflammatory diseases. We will discuss strategies to target this novel level of gene regulation for therapeutic effect and review exciting preliminary studies that underscore its potential for treating neurological disorders.

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lncRNA MEG3 restrained the M1 polarization of microglia in acute spinal cord injury through the HuR/A20/NF‐κB axis

Cited by 9 publications

References 51 publications

LncRNA MEG3 Reduces the Ratio of M2/M1 Macrophages Through the HuR/CCL5 Axis in Hepatocellular Carcinoma

LncRNA MEG3 Reduces the Ratio of M2/M1 Macrophages Through the HuR/CCL5 Axis in Hepatocellular Carcinoma

Electroacupuncture Relieves HuR/KLF9-Mediated Inflammation to Enhance Neurological Repair after Spinal Cord Injury

RNA regulation of inflammatory responses in glia and its potential as a therapeutic target in central nervous system disorders

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