MicroRNA-15b Suppresses Th17 Differentiation and Is Associated with Pathogenesis of Multiple Sclerosis by Targeting <i>O</i>-GlcNAc Transferase

Liu, Ruiqiong; Ma, Xiaofeng; Chen, Li; Yang, Yang; Zeng, Yi; Gao, Jie; Jiang, Wei; Zhang, Fang; Li, Daojing; Han, Bin; Han, Ranran; Qiu, Rongfang; Huang, Wei; Wang, Yan; Hao, Junwei

doi:10.4049/jimmunol.1601727

Cited by 66 publications

(53 citation statements)

References 73 publications

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“…In the IL-17 signaling pathway, several miRNAs, including miR-23a, miRNA cluster 106a-363, miR-181a-5p, miR-15b, and miR-155, have been found to target signaling intermediates [24-27]. In this study, we further demonstrated that miR-135a expression was significantly lower in the NPC cells compared to that of normal cells, and found that miR-135a potentially targets IL-17, in that the 3′UTR of IL-17 mRNA contains the binding sequence for miR-135a.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-135a Inhibits Nasopharyngeal Carcinoma Cell Proliferation Through Targeting Interleukin-17

Wang

Kang

Yang

et al. 2018

Cell Physiol Biochem

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Background/Aims: The objective of this study was to investigate the potential role of IL-17 in the development of nasopharyngeal carcinoma (NPC) and to screen microRNAs (miRNAs) that potentially target IL-17 in NPC cells. Methods: Blood was collected from NPC patients and normal subjects, and plasma IL-17 concentration was quantified by enzyme-linked immunosorbent assay. An immortalized normal human nasopharyngeal epithelial cell line, NP69, was treated with or without human IL-17 (15 ng/mL) for various times, and expression of IL-1ß, IL-6, IL-12, and TNF-α mRNA was assessed by real-time reverse transcription PCR. The candidate miRNAs that potentially target IL-17 were predicted by a bioinformatics strategy. The selected miR-135a mimic was transfected into primary NPC cells, and cell proliferation was assessed by MTT assay. Results: The concentration of plasma IL-17 was significantly higher in the NPC patients (92.5 ± 7.3 pg/mL) than in the control subjects (56.8 ± 2.9 pg/mL). In response to IL-17 treatment, the mRNA expression of IL-1ß and IL-6 was significantly upregulated and reached a peak at 12 h, followed by a slight decrease at 24 h, while the mRNA expression of IL-12 and TNF-α was significantly upregulated at 12 h and remained high even at 48 h after exposure to IL-17. Moreover, miR-135a specifically targets IL-17 and was dramatically downregulated in NPC cells compared with NP69 cells. Transfection of exogenous miR-135a mimic resulted in significant suppression of IL-17 secretion and subsequent inhibition of NPC cell proliferation. Conclusions: Blood IL-17 was significantly higher in NPC patients compared with normal subjects. Expression of miR-135a in the cancer cells isolated from nasopharyngeal tumors was significantly lower than that in NP69 cells, and suppression of IL-17 by miR-135a mimic resulted in significant inhibition of NPC cell proliferation. These findings suggested that downregulation of miR-135a may contribute to the development of NPC via the mechanism of IL-17 stimulation of proinflammatory cytokine expression.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-135a Inhibits Nasopharyngeal Carcinoma Cell Proliferation Through Targeting Interleukin-17

Wang

Kang

Yang

et al. 2018

Cell Physiol Biochem

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“…The X-linked OGT gene is hypomethylated in T cells from female patients with systemic lupus erythematosus, an auto-immune disease with a high prevalence especially in females mediated in part by Th1 and Th17 cells (Hewagama et al 2013). Additionally, miRNA15-b targeting of OGT transcripts was recently found to be down-regulated in T cells from multiple sclerosis patients, resulting in increased Th17 differentiation (Liu et al 2017). ELF-1, a transcription factor for the TCR ζ chain gene, requires O-GlcNAcylation and phosphorylation to translocate from the cytoplasm to the nucleus.…”

Section: O-glcnac In T Cell Mediated Diseasesmentioning

confidence: 99%

O-GlcNAc: a novel regulator of immunometabolism

Machacek

Slawson

Fields

2018

J Bioenerg Biomembr

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The rapidly expanding field of immunometabolism focuses on how metabolism controls the function of immune cells. CD4 T cells are essential for the adaptive immune response leading to the eradication of specific pathogens. However, when T cells are inappropriately over-active, they can drive autoimmunity, allergic disease, and chronic inflammation. The mechanisms by which metabolic changes influence function in CD4 T cells are not fully understood. The post-translational protein modification, O-GlcNAc (O-linked β-N-acetylglucosamine), dynamically cycles on and off of intracellular proteins as cells respond to their environment and flux through metabolic pathways changes. As the rate of O-GlcNAc cycling fluctuates, protein function, stability, and/or localization can be affected. Thus, O-GlcNAc is critically poised at the nexus of cellular metabolism and function. This review highlights the intra- and extracellular metabolic factors that influence CD4 T cell activation and differentiation and how O-GlcNAc regulates these processes. We also propose areas of future research that may illuminate O-GlcNAc's role in the plasticity and pathogenicity of CD4 T cells and uncover new potential therapeutic targets.

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“…The most consistently upregulated miRNAs in MS include miR-142-3p, miR-146a/b and miR-155, while family members of miR-15, miR-548 and let-7 exhibit downregulation 8 . Functionally, these miRNAs have been implicated in immune processes including differentiation and function of CD4 + T helper cells 9,10,11 . Other miRNAs, such as miR-150 and miR-181c, which are upregulated in MS, have been proposed as biomarkers of different stages of disease, including early active MS 12,13 .…”

Section: Introductionmentioning

confidence: 99%

Profiling of small non-coding RNAs across cellular and biofluid compartments: implications for multiple sclerosis immunopathology

Zheleznyakova

Piket

Needhamsen

et al. 2020

Preprint

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Multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system (CNS), is associated with dysregulation of microRNAs (miRNA). We here analyzed all classes of small non-coding RNAs (sncRNAs) in matching peripheral blood mononuclear cells (PBMCs), plasma, cerebrospinal fluid (CSF) cells and cell-free CSF from relapsing-remitting (RRMS, n=12 in relapse, n=11 in remission), secondary progressive (SPMS, n=6) MS patients and noninflammatory and inflammatory neurological disease controls (NINDC, n=11; INDC, n=5). We show widespread changes in small nuclear, nucleolar, transfer RNAs and miRNAs. In CSF cells, 133/133 and 115/117 differentially expressed sncRNAs are increased in RRMS relapse compared to remission and RRMS compared to NINDC, respectively. In contrast, 65/67 differentially expressed PBMC sncRNAs are decreased in RRMS compared to NINDC. The striking contrast between periphery and CNS suggests that sncRNA-mediated mechanisms, including alternative splicing, RNA degradation and mRNA translation, regulate the transcriptome of pathogenic cells primarily in the target organ.

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MicroRNA-15b Suppresses Th17 Differentiation and Is Associated with Pathogenesis of Multiple Sclerosis by Targeting O-GlcNAc Transferase

Cited by 66 publications

References 73 publications

MicroRNA-135a Inhibits Nasopharyngeal Carcinoma Cell Proliferation Through Targeting Interleukin-17

MicroRNA-135a Inhibits Nasopharyngeal Carcinoma Cell Proliferation Through Targeting Interleukin-17

O-GlcNAc: a novel regulator of immunometabolism

Profiling of small non-coding RNAs across cellular and biofluid compartments: implications for multiple sclerosis immunopathology

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