Next-generation sequencing reveals broad down-regulation of microRNAs in secondary progressive multiple sclerosis CD4+ T cells

Sanders, Katherine A.; Benton, Miles C.; Lea, Rodney Arthur; Maltby, Vicki E.; Agland, Susan; Griffin, Nathan; Scott, Rodney J.; Tajouri, Lotti; Lechner‐Scott, Jeannette

doi:10.1186/s13148-016-0253-y

Cited by 46 publications

(38 citation statements)

References 35 publications

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“…A downside expression of SOCS6 was discovered in periodontal disease [18]. Also, the targeted evidence about miR-142-3p vs. SOCS6 was reported in CD4þ T cells of multiple sclerosis [19] and in nasopharyngeal carcinoma [20]. We discovered that SOCS6 was a possible target of miR-142-3p (http://www.targetscan.org/cgi-bin/targetscan/vert_71/) using TargetScan (version 7.1).…”

Section: Socs6 Is Targeted By Mir-142-3pmentioning

confidence: 97%

Abnormal expression of long noncoding RNA FGD5-AS1 affects the development of periodontitis through regulating miR-142-3p/SOCS6/NF-κB pathway

Chen

Ze-dong

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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Periodontitis refers to the inflammation of gums and the surrounding structures and caused by a bacterial infection. The infection occurs owing to poor oral hygiene and could destroy the bone and the gum over time if left untreated. The present study identified the involvement of a key long noncoding RNA (lncRNA), i.e. FGD5-AS1, in the pathogenesis of periodontitis by assessing its expression in the gingival tissues of patients diagnosed with chronic periodontitis (CP). Overexpression of FGD5-AS1 in primary human periodontal ligament cells (PDLCs) significantly reduced the lipopolysaccharide (LPS)induced periodontitis, whereas its suppression aggravated this injury. Moreover, the miR-142-3p was markedly expressed in the gingival samples of patients diagnosed with CP and LPS-induced PDLCs. We found that the FGD5-AS1-mediated reduction in the inflammation was mediated through downside regulation of miR-142-3p, as evident from the upregulation of SOCS6, a target gene of miR-142-3p. Furthermore, the association between FGD5-AS1 and NF-jB pathway was detected. FGD5-AS1 was found to protect against LPS-stimulated PDLC injury through restraining the NF-jB signals. Based on these findings, we conclude that up-regulation of lncRNA FGD5-AS1 could protect against periodontitis via regulating the miR-142-3p/SOCS6/NF-jB signals. Therefore, the FGD5-AS1/miR-142-3p/SOCS6 axis may act as an important indicator in explaining the pathogenesis of periodontitis.

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Section: Socs6 Is Targeted By Mir-142-3pmentioning

confidence: 97%

Abnormal expression of long noncoding RNA FGD5-AS1 affects the development of periodontitis through regulating miR-142-3p/SOCS6/NF-κB pathway

Chen

Ze-dong

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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“…To date, the most abundantly studied class of these exRNAs are microRNAs (miRNA), which have been implicated in a wide range of diseases including heart failure [1, 2], cancer [3, 4], and multiple sclerosis [5, 6]. miRNAs are small, non-coding RNAs that have the ability to regulate whole networks of genes through transcriptional and translational regulation.…”

Section: Introductionmentioning

confidence: 99%

High Throughput Sequencing of Extracellular RNA from Human Plasma

et al. 2017

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The presence and relative stability of extracellular RNAs (exRNAs) in biofluids has led to an emerging recognition of their promise as ‘liquid biopsies’ for diseases. Most prior studies on discovery of exRNAs as disease-specific biomarkers have focused on microRNAs (miRNAs) using technologies such as qRT-PCR and microarrays. The recent application of next-generation sequencing to discovery of exRNA biomarkers has revealed the presence of potential novel miRNAs as well as other RNA species such as tRNAs, snoRNAs, piRNAs and lncRNAs in biofluids. At the same time, the use of RNA sequencing for biofluids poses unique challenges, including low amounts of input RNAs, the presence of exRNAs in different compartments with varying degrees of vulnerability to isolation techniques, and the high abundance of specific RNA species (thereby limiting the sensitivity of detection of less abundant species). Moreover, discovery in human diseases often relies on archival biospecimens of varying age and limiting amounts of samples. In this study, we have tested RNA isolation methods to optimize profiling exRNAs by RNA sequencing in individuals without any known diseases. Our findings are consistent with other recent studies that detect microRNAs and ribosomal RNAs as the major exRNA species in plasma. Similar to other recent studies, we found that the landscape of biofluid microRNA transcriptome is dominated by several abundant microRNAs that appear to comprise conserved extracellular miRNAs. There is reasonable correlation of sets of conserved miRNAs across biological replicates, and even across other data sets obtained at different investigative sites. Conversely, the detection of less abundant miRNAs is far more dependent on the exact methodology of RNA isolation and profiling. This study highlights the challenges in detecting and quantifying less abundant plasma miRNAs in health and disease using RNA sequencing platforms.

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“…Sanders et al recently compared miRNA profiles of CD4 T cells from patients with secondary progressive MS with healthy donors. Results obtained by NGS and validated by RT-qPCR identified several miRNAs specifically downregulated in MS CD4 T cells, with the suppressor of cytokine signalling 6 (SOCS6) being one gene targeted by eight of ten of the identified miRNAs [76]. Moreover, genomewide DNA methylation studies have identified DMRs of CD4 T cells in MS patients compared to healthy controls, specifically on chromosome 6p21 at HLA-DRB1 (a known MS risk locus), and additional non-HLA CpGs that localized to Figure 3 The importance of epigenetic mechanisms for regulatory T cells.…”

Section: Epigenetics Of T Cells In Autoimmunitymentioning

confidence: 95%

Stochastics of Cellular Differentiation Explained by Epigenetics: The Case of T‐Cell Differentiation and Functional Plasticity

et al. 2017

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Epigenetic marks including histone modifications and DNA methylation are associated with the regulation of gene expression and activity. In addition, an increasing number of non-coding RNAs with regulatory activity on gene expression have been identified. Alongside, technological advancements allow for the analysis of these mechanisms with high resolution up to the single-cell level. For instance, the assay for transposase-accessible chromatin using sequencing (ATAC-seq) simultaneously probes for chromatin accessibility and nucleosome positioning. Thus, it provides information on two levels of epigenetic regulation. Development and differentiation of T cells into functional subset cells including memory T cells are dynamic processes driven by environmental signals. Here, we briefly review the current knowledge of how epigenetic regulation contributes to subset specification, differentiation and memory development in T cells. Specifically, we focus on epigenetic mechanisms differentially active in the two distinct T cell populations expressing ab or cd T cell receptors. We also discuss examples of epigenetic alterations of T cells in autoimmune diseases. DNA methylation and histone acetylation are subject to modification by several classes of 'epigenetic modifiers', some of which are in clinical use or in preclinical development. Therefore, we address the impact of some epigenetic modifiers on T-cell activation and differentiation, and discuss possible synergies with T cellbased immunotherapeutic strategies.

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Next-generation sequencing reveals broad down-regulation of microRNAs in secondary progressive multiple sclerosis CD4+ T cells

Cited by 46 publications

References 35 publications

Abnormal expression of long noncoding RNA FGD5-AS1 affects the development of periodontitis through regulating miR-142-3p/SOCS6/NF-κB pathway

Abnormal expression of long noncoding RNA FGD5-AS1 affects the development of periodontitis through regulating miR-142-3p/SOCS6/NF-κB pathway

High Throughput Sequencing of Extracellular RNA from Human Plasma

Stochastics of Cellular Differentiation Explained by Epigenetics: The Case of T‐Cell Differentiation and Functional Plasticity

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