Identification of the miRNA–mRNA regulatory network in multiple sclerosis

Yang, Qi; Wei, Pan; Qian, Liwei

doi:10.1080/01616412.2016.1250857

Cited by 46 publications

(36 citation statements)

References 42 publications

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“…There was a report showed that miR-20a-5p could be used as biomarker in the treatment response of naive patients with relapsing remitting MS with interferon-β (IFN-β) 17. These findings also suggested that miR-20a-5p might be an important player in the pathophysiology of MS 18. Since the role of miR-20a-5p in uveitis is not completely clarified, we determined to investigate the expression pattern and role of this molecule in VKH disease.…”

Section: Introductionmentioning

confidence: 97%

MicroRNA-20a-5p suppresses IL-17 production by targeting OSM and CCL1 in patients with Vogt-Koyanagi-Harada disease

Chang

Tan

et al. 2017

Br J Ophthalmol

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Aim To elucidate the role of microRNA-20a-5p (miR20a-5p) in the pathogenesis of Vogt-Koyanagi-Harada (VKH) disease. Methods Quantitative real-time PCR was used to quantify miR-20a-5p expression in CD4 + T cells from patients with active VKH and normal controls. The promoter methylation status of miR-20a-5p was detected by bisulfite sequencing PCR. Targets were evaluated by a luciferase reporter assay. The functional effects of miR-20a-5p on CD4 + T cells from patients with active VKH were assessed by upregulation or downregulation of its expression using liposomes. results The miR-20a-5p level was significantly decreased in CD4 + T cells from patients with active VKH as compared with normal controls. The two genes, oncostatin M (OSM) and C-C motif chemokine ligand 1 (CCL1), were identified as targets of miR-20a-5p. The upregulation of miR-20a-5p significantly suppressed interleukin 17 (IL-17) production in CD4 + T cells from patients with active VKH, whereas downregulation of miR-20a-5p exhibited an inverse effect. In addition, overexpression of OSM and CCL1 could rescue the effect of the upregulation of miR-20a-5p. Moreover, the level of miR-20a-5p was reduced in response to hypermethylation of the promoter. Further study showed that miR-20a-5p suppressed the activity of the phosphoinositide 3-kinase-AKT pathway. Conclusions Our findings indicate that downregulation of miR-20a-5p is caused by promoter hypermethylation. MiR-20a-5p could also suppress the production of IL-17 by targeting OSM and CCL1 production in CD4 + T cells in patients with active VKH.

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Section: Introductionmentioning

confidence: 97%

MicroRNA-20a-5p suppresses IL-17 production by targeting OSM and CCL1 in patients with Vogt-Koyanagi-Harada disease

Chang

Tan

et al. 2017

Br J Ophthalmol

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“…MS is thought to result from a complex interplay of genetic, epigenetic, and environmental risk factors . MicroRNAs (miRNAs) are epigenetic factors that have been investigated in MS, and over 170 miRNAs have been found to be differentially expressed in various tissues in either adult‐onset MS or experimental autoimmune encephalomyelitis (EAE) in mice . One study specifically compared miRNA expression levels in ped‐MS cases to pediatric controls, and 12 upregulated and one downregulated miRNA were reported .…”

Section: Introductionmentioning

confidence: 99%

miRNAcontributions to pediatric‐onset multiple sclerosis inferred fromGWAS

Rhead

Shao

Graves

et al. 2019

Ann Clin Transl Neurol

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Objective Onset of multiple sclerosis (MS) occurs in childhood for approximately 5% of cases (pediatric MS, or ped‐MS). Epigenetic influences are strongly implicated in MS pathogenesis in adults, including the contribution from microRNAs (miRNAs), small noncoding RNAs that affect gene expression by binding target gene mRNAs. Few studies have specifically examined miRNAs in ped‐MS, but individuals developing MS at an early age may carry a relatively high burden of genetic risk factors, and miRNA dysregulation may therefore play a larger role in the development of ped‐MS than in adult‐onset MS. This study aimed to look for evidence of miRNA involvement in ped‐MS pathogenesis. Methods GWAS results from 486 ped‐MS cases and 1362 controls from the U.S. Pediatric MS Network and Kaiser Permanente Northern California membership were investigated for miRNA‐specific signals. First, enrichment of miRNA‐target gene network signals was evaluated using MIGWAS software. Second, SNPs in miRNA genes and in target gene binding sites (miR−SNPs) were tested for association with ped‐MS, and pathway analysis was performed on associated target genes. Results MIGWAS analysis showed that miRNA‐target gene signals were enriched in GWAS (P = 0.038) and identified 39 candidate biomarker miRNA‐target gene pairs, including immune and neuronal signaling genes. The miR‐SNP analysis implicated dysregulation of miRNA binding to target genes in five pathways, mainly involved in immune signaling. Interpretation Evidence from GWAS suggests that miRNAs play a role in ped‐MS pathogenesis by affecting immune signaling and other pathways. Candidate biomarker miRNA‐target gene pairs should be further studied for diagnostic, prognostic, and/or therapeutic utility.

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“…To conceptually analyze and intuitively visualize interactions in such a vast regulatory network, the construction of a molecular interaction map is the first step in modern biological studies 19,20 . A number of comprehensive regulatory maps have been constructed to help in the understanding of the mechanisms underlying complex biological systems [21][22][23][24] , however, only a handful of attempts have been made so far to develop a mechanistic understanding of complex inflammatory disorders through the investigation of underlying molecular interaction maps [25][26][27][28] .…”

Section: Problem and Research Gapmentioning

confidence: 99%

The Atlas of Inflammation-Resolution (AIR)

Serhan

Gupta

Perretti

et al. 2020

Preprint

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Acute inflammation is a protective reaction by the immune system in response to invading pathogens or tissue damage. Ideally, the response should be localized, self-limited, and returning to homeostasis. If not resolved, acute inflammation can result in organ pathologies leading to chronic inflammatory phenotypes. Acute inflammation and inflammation resolution are complex coordinated processes, involving a number of cell types, interacting in space and time. The biomolecular complexity and the fact that several biomedical fields are involved, make a multi and interdisciplinary approach necessary. This Atlas of Inflammation Resolution (AIR) is a web-based resource capturing the state-of-theart in acute inflammation and inflammation resolution research. The AIR provides an interface for users to search thousands of interactions, arranged in inter-connected multi-layers of process diagrams, covering a wide range of clinically relevant phenotypes. The AIR serves as an open access knowledgebase, including a gateway to numerous public databases. It is furthermore possible for the user to map experimental data onto the molecular interaction maps of the AIR, providing the basis for bioinformatics analyses and systems biology approaches. By mapping experimental data onto the Atlas, it can be used to elucidate drug action as well as molecular mechanisms underlying different disease phenotypes. For the visualization and exploration of information, the AIR uses the Minerva platform, which is a well-established tool for the presentation of disease maps. The molecular details of the AIR are encoded using international standards.The Atlas of Inflammation Resolution was created as a freely accessible resource, supporting research and education in the fields of acute inflammation and inflammation resolution. The AIR connects research communities, facilitates clinical decision making, and supports research scientists in the formulation and validation of hypotheses. Abbreviations:

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Identification of the miRNA–mRNA regulatory network in multiple sclerosis

Abstract: hsa-miR-30a, hsa-miR-93, hsa-miR-20b, and hsa-miR-20a might be the key participant in the pathophysiology of MS involved in signaling pathways including ribosome, tuberculosis, and pathways in cancer.

Cited by 46 publications

References 42 publications

MicroRNA-20a-5p suppresses IL-17 production by targeting OSM and CCL1 in patients with Vogt-Koyanagi-Harada disease

MicroRNA-20a-5p suppresses IL-17 production by targeting OSM and CCL1 in patients with Vogt-Koyanagi-Harada disease

miRNAcontributions to pediatric‐onset multiple sclerosis inferred fromGWAS

The Atlas of Inflammation-Resolution (AIR)

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