Analysis of microRNA and Gene Expression Profiles in Multiple Sclerosis: Integrating Interaction Data to Uncover Regulatory Mechanisms

Freiesleben, Sherry; Hecker, Michael; Zettl, Uwe K.; Fuellen, Georg; Taher, Leila

doi:10.1038/srep34512

Cited by 61 publications

(45 citation statements)

References 78 publications

(93 reference statements)

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“…Experimental disruptions of miRNA genes amount to diverse abnormal phenotypes, including defects in the thymus, hematopoietic lineages, and brain, altered susceptibility to infections, and autoimmune-mediated diseases (7). For example, the miRNAs miR-20b-5p, miR-30a-5p, and miR-146a-5p are dysregulated in immunological and neurologic pathways in MS (22), and the miRNA levels in peripheral blood cells of MS patients change in response to IFN-b treatment (23).…”

Section: Regulation Of Inflammasomesmentioning

confidence: 99%

Dysregulation of Inflammasome Priming and Activation by MicroRNAs in Human Immune-Mediated Diseases

Boxberger

Hecker

Zettl

2019

The Journal of Immunology

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Inflammasomes are protein complexes that respond to a wide range of pathogens and cellular damage signals. Their activation prompts the caspase-1–mediated cleavage of the proinflammatory cytokines IL-1β and IL-18. Inflammasome dysregulation has been demonstrated to play a role in a range of diseases involving the adaptive immune system like multiple sclerosis, rheumatic diseases, and type 1 diabetes. Priming and activation of inflammasomes can be modulated by microRNAs (miRNAs), small noncoding RNAs that regulate gene expression posttranscriptionally. miRNAs, such as miR-223-3p, have been demonstrated to directly target the inflammasome components NLRP3, caspase-1, and caspase-8. Other miRNAs like miR-155-5p modulate TLR-, IL-1R–, TNFR-, and IFNAR-mediated signaling pathways upstream of the inflammasomes. In this study, we discuss how a more detailed elucidation of miRNA-driven inflammasome regulation helps in understanding the molecular processes underlying immune-mediated human diseases, holds potential for the identification of biomarkers and may offer novel targets for the development of future therapeutics.

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Section: Regulation Of Inflammasomesmentioning

confidence: 99%

Dysregulation of Inflammasome Priming and Activation by MicroRNAs in Human Immune-Mediated Diseases

Boxberger

Hecker

Zettl

2019

The Journal of Immunology

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“…12,13 For example, in the collagen, antibody induced arthritis mouse model of RA, shikonin can suppress the inflammation by targeting specific lncRNAs, 14 and in presence of quercetin, the apoptosis of fibroblast-like synoviocytes (FLS) in RA was also blocked, in which the involvement of lncRNA MALAT1 plays a critical role. [15][16][17][18][19][20][21][22] In this study, we attempted to discover how MEG3 affects the proliferation and inflammation of LPS-treated chondrocytes in RA.…”

Section: Introductionmentioning

confidence: 99%

LncRNA MEG3 inhibits rheumatoid arthritis through miR‐141 and inactivation of AKT/mTOR signalling pathway

Liu

Meng

et al. 2019

J Cellular Molecular Medi

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Rheumatoid arthritis (RA) is a chronic inflammation mediated by autoimmune responses. MEG3, a kind of long noncoding RNA (lncRNA), participates in cell proliferation in cancer tissues. However, the correlation between MEG3 and RA is yet unclear. Therefore, to clarify how MEG3 works in RA, we performed a series of experiments using RA samples. We found that MEG3 was downregulated in the fibroblast‐like synoviocytes of RA patients (RA‐FLS), in comparison with healthy subjects. MEG3 was also down‐regulated evidently in lipopolysaccharide (LPS)‐treated chondrocyte. As part of our experiments, MEG3 was overexpressed in chondrocyte by transfection with lentivirus containing sequences encoding MEG3. In addition, in presence of LPS, reductions were identified not only in the cell proliferation, but also in the generation of interleukin‐23 (IL‐23), which, however were reversed in the lentivirus (containing MEG3‐encoding sequences)‐transfected chondrocytes. Up‐regulated MEG3 resulted in an increase the level of Ki67. Moreover, MEG3 was negatively correlated with miR‐141, and miR‐141 was up‐regulated in LPS‐treated chondrocyte. Inhibitory effects of MEG3 overexpression, mentioned above, were partially abolished by overexpressed miR‐141. Further, animal experiment also showed the inhibitory effect of MEG3 in overexpression on the AKT/mTOR signaling pathway. In‐vivoexperiments also showed that cell proliferation was facilitated by MEG3 overexpression with inhibited inflammation. In summary, the protective role of MEG3 in RA was proved to be exerted by the increase in the rate of proliferation, which might correlate to the regulatory role of miR‐141 and AKT/mTOR signal pathway, suggesting that MEG3 holds great promise as a therapeutic strategy for RA.

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“…MiRNAs post-transcriptionally regulate the degradation and translation of their target genes. MiRNAs are involved in the inflammatory response and the development of autoimmune diseases, such as rheumatoid arthritis [14], and multiple sclerosis [15]. Increasing evidence has shown that aberrant miRNA expression is linked to the regulation of autophagy [16].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-199a-5p Induced Autophagy and Inhibits the Pathogenesis of Ankylosing Spondylitis by Modulating the mTOR Signaling via Directly Targeting Ras Homolog Enriched in Brain (Rheb)

Wang

Luo

Wang

et al. 2017

Cell Physiol Biochem

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Background/Aims: Ankylosing spondylitis (AS) is an inflammatory and immune disease leading to disability. Autophagy has been identified as a potential player in understanding the pathogenesis of AS. Methods: MiRNA-199a-5p and autophagy-related gene expression were determined by qRT-PCR or Western blot. Cytokine production was determined using ELISA assays. Proliferation was determined by MTT assay. MiRNA-199a-5p and Ras homolog enriched in brain (Rheb) were upregulated or downregulated by overexpression of plasmid or siRNA transfection. Results: Expression of miRNA-199a-5p, and autophagy-related genes LC3, beclin1, and ATG5 was significantly decreased in T cells of AS patients. Serum concentrations of TNF-α, IL-17, and IL-23 were promoted in AS patients, compared to healthy controls. MiRNA-199a-5p expression levels also showed significant negative correlations with the Ankylosing Spondylitis Disease Activity Score (ASDAS) and modified Stoke Ankylosing Spon dylitis Spinal Score (mSASSS) of AS patients. In Jurkat T cells and T cells isolated from AS patients, miRNA-199a-5p overexpression promoted autophagy-related genes expression and decreased TNF-α, IL-17, and IL-23 levels, whereas inhibition of miRNA-199a-5p attenuated these effects. As a direct target of miRNA-199a-5p, Rheb inhibition led to a striking decrease in the phosphorylation of the mechanistic target of rapamycin (mTOR) and induced autophagy. Moreover, pcDNA3.1-Rheb effectively reduced the inhibiting effects of mTOR signaling caused by miRNA-199a-5p overexpression. All effects were offset by pretreating with rapamycin (an mTOR antagonist). Conclusions: AS patients with advanced spinal damage had decreased autophagy levels and that miRNA-199a-5p may induce autophagy and inhibit the pathogenesis of AS by modulating the mTOR signaling via direct targeting Rheb.

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Analysis of microRNA and Gene Expression Profiles in Multiple Sclerosis: Integrating Interaction Data to Uncover Regulatory Mechanisms

Cited by 61 publications

References 78 publications

Dysregulation of Inflammasome Priming and Activation by MicroRNAs in Human Immune-Mediated Diseases

Dysregulation of Inflammasome Priming and Activation by MicroRNAs in Human Immune-Mediated Diseases

LncRNA MEG3 inhibits rheumatoid arthritis through miR‐141 and inactivation of AKT/mTOR signalling pathway

MicroRNA-199a-5p Induced Autophagy and Inhibits the Pathogenesis of Ankylosing Spondylitis by Modulating the mTOR Signaling via Directly Targeting Ras Homolog Enriched in Brain (Rheb)

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