scholarly journals Epigenetic Regulation Mediated by miRNA in the Susceptibility and Pathogenesis of Rheumatoid Arthritis

2020 ◽  
Author(s):  
Shicheng Guo ◽  
Cen Chang ◽  
Lingxia Xu ◽  
Runrun Zhang ◽  
Yehua Jin ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Therapeutic Intervention ◽  
Target Genes ◽  
Cell Types ◽  
Micro Rna ◽  
Current Evidence ◽  
Diagnosis And Prognosis ◽  
Transcriptome Regulation ◽  
Therapy Target ◽  
Different Cell Types

micro-RNA (miRNA) has been demonstrated to play important roles in the transcriptome regulation and disease development including cancer and autoimmune disease such as rheumatoid arthritis. However, a comprehensive map on how the mRNAs regulate transcripts, pathways, immune system differentiation and interaction with terminal cells like T-cells, fibroblast-like synoviocytes (FLS), osteoblast and osteoclast still unknown. In this review, we have provided a thorough summary on the roles of miRNAs in the susceptibility, pathogenesis, diagnosis, therapeutic intervention and prognosis. Numerous miRNAs were found abnormally expressed in rheumatoid arthritis relevant cells and regulated the target genes and pathways like NF-κB, Fas-FasL, JAK-STAT, IRE1-RIDD, mTOR pathway. In addition, miRNA act as gene expression regulators affect the T-cell differentiate to different cell types including Th17 and T-reg cells which provide promising gene therapy target to regulate immune systems in rheumatoid arthritis. We also summarized interesting diagnosis and prognosis roles of blood and cell-free based miRNAs which provided novel opportunity to work together with rheumatoid factors (RF), anti-CCP to provide accurate diagnosis and prognosis especially for seronegative patients. Furthermore, functional genetic variants in miRNA-499 and miRNA-146a explained part of missing susceptibility of rheumatoid arthritis. Finally, miRNAs were showed as promising biomarker to indicate the DMRDS and immunotherapy efficiency, drug response and resistance. What’s more, autotherapeutic effect of miRNA intervention provided promising to develop miRNA based rheumatoid arthritis drugs. Overall, current evidence supports miRNAs as the interesting targets to better understand the pathogenetic mechanism and therapeutic intervention of rheumatoid arthritis.

scholarly journals Epigenetic Regulation Mediated by microRNAs in the Susceptibility and Pathogenesis of Rheumatoid Arthritis

2020 ◽  
Author(s):  
Shicheng Guo ◽  
Cen Chang ◽  
Lingxia Xu ◽  
Runrun Zhang ◽  
Yehua Jin ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Immune System ◽  
Target Genes ◽  
Cell Types ◽  
Therapeutic Interventions ◽  
Current Evidence ◽  
The Novel ◽  
Diagnosis And Prognosis ◽  
Therapy Targets ◽  
System Differentiation

MicroRNAs (miRNAs) play crucial roles in the regulation of the transcriptome and development of diseases including cancer and autoimmune diseases, such as rheumatoid arthritis (RA). Currently, a comprehensive map, illustrating how miRNAs regulate transcripts, pathways, immune system differentiation, and their interaction with terminal cells, such as T cells, fibroblast-like synoviocytes (FLS), osteoblasts, and osteoclasts, is still missing. In this review, we provide a thorough summary of the roles of miRNAs in the susceptibility to pathogenesis, diagnosis, therapeutic intervention, and prognosis of RA. Numerous miRNAs are abnormally expressed in cells involved in RA, and regulate target genes and pathways including the NF-κB, Fas-FasL, JAK-STAT, IRE1-RIDD, and mTOR pathways. By regulating gene expression, miRNAs affect T cell differentiation to diverse cell types, including Th17 and T-reg cells, and thus constitute promising gene therapy targets to modulate the immune system in RA. We summarize the diagnostic and prognostic potential of blood-circulating and cell-free miRNAs, highlighting the novel opportunities to combine these with rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) to provide accurate diagnosis and prognosis, especially for seronegative patients. Furthermore, we outline how functional genetic variants of miR-499 and miR-146a partly explain the unmet susceptibility to RA. Additionally, we review the evidence implicating miRNAs as promising biomarkers of efficiency, response, and resistance to disease-modifying anti-rheumatic drugs (DMRDs) and immunotherapy. Finally, we discuss the autotherapeutic effect of miRNA intervention as a step toward the development of miRNA-based anti-RA drugs. Collectively, the current evidence supports miRNAs as interesting targets to better understand the pathogenetic mechanisms of RA and design more efficient therapeutic interventions.

scholarly journals From Rheumatoid Factor to Anti-Citrullinated Protein Antibodies and Anti-Carbamylated Protein Antibodies for Diagnosis and Prognosis Prediction in Patients with Rheumatoid Arthritis

2021 ◽  
Vol 22 (2) ◽  
pp. 686
Author(s):  
Chao-Yi Wu ◽  
Huang-Yu Yang ◽  
Shue-Fen Luo ◽  
Jenn-Haung Lai
Keyword(s):  
Rheumatoid Arthritis ◽  
Treatment Options ◽  
Clinical Manifestations ◽  
Bone Destruction ◽  
Response To Therapy ◽  
Current Evidence ◽  
Prognosis Prediction ◽  
Diagnosis And Prognosis ◽  
Systemic Inflammatory Disease ◽  
Citrullinated Protein

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease mainly involving synovial inflammation and articular bone destruction. RA is a heterogeneous disease with diverse clinical presentations, prognoses and therapeutic responses. Following the first discovery of rheumatoid factors (RFs) 80 years ago, the identification of both anti-citrullinated protein antibodies (ACPAs) and anti-carbamylated protein antibodies (anti-CarP Abs) has greatly facilitated approaches toward RA, especially in the fields of early diagnosis and prognosis prediction of the disease. Although these antibodies share many common features and can function synergistically to promote disease progression, they differ mechanistically and have unique clinical relevance. Specifically, these three RA associating auto-antibodies (autoAbs) all precede the development of RA by years. However, while the current evidence suggests a synergic effect of RF and ACPA in predicting the development of RA and an erosive phenotype, controversies exist regarding the additive value of anti-CarP Abs. In the present review, we critically summarize the characteristics of these autoantibodies and focus on their distinct clinical applications in the early identification, clinical manifestations and prognosis prediction of RA. With the advancement of treatment options in the era of biologics, we also discuss the relevance of these autoantibodies in association with RA patient response to therapy.

Dpp signaling thresholds in the dorsal ectoderm of the Drosophila embryo

Development ◽  
2000 ◽  
Vol 127 (15) ◽  
pp. 3305-3312 ◽  
Author(s):  
H.L. Ashe ◽  
M. Mannervik ◽  
M. Levine
Keyword(s):  
Gene Expression ◽  
Target Genes ◽  
Histone Acetyltransferase ◽  
Cell Types ◽  
Drosophila Embryo ◽  
Present Evidence ◽  
Drosophila Homolog ◽  
Dorsal Ectoderm ◽  
Transgenic Embryos ◽  
Different Cell Types

The dorsal ectoderm of the Drosophila embryo is subdivided into different cell types by an activity gradient of two TGF(β) signaling molecules, Decapentaplegic (Dpp) and Screw (Scw). Patterning responses to this gradient depend on a secreted inhibitor, Short gastrulation (Sog) and a newly identified transcriptional repressor, Brinker (Brk), which are expressed in neurogenic regions that abut the dorsal ectoderm. Here we examine the expression of a number of Dpp target genes in transgenic embryos that contain ectopic stripes of Dpp, Sog and Brk expression. These studies suggest that the Dpp/Scw activity gradient directly specifies at least three distinct thresholds of gene expression in the dorsal ectoderm of gastrulating embryos. Brk was found to repress two target genes, tailup and pannier, that exhibit different limits of expression within the dorsal ectoderm. These results suggest that the Sog inhibitor and Brk repressor work in concert to establish sharp dorsolateral limits of gene expression. We also present evidence that the activation of Dpp/Scw target genes depends on the Drosophila homolog of the CBP histone acetyltransferase.

Analysis of Predictive Value and Target Gene Prediction of Serum Micro-RNA-205 in Diagnosis and Prognosis of Prostate Cancer

2020 ◽  
Vol 12 (2) ◽  
pp. 196-201
Author(s):  
Xiangnan Hu ◽  
Xiaoliang Dou ◽  
He Wang ◽  
Jinbo Sun ◽  
Bo Zhang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Mirna Expression ◽  
Predictive Value ◽  
Expression Profiling ◽  
Target Genes ◽  
Micro Rna ◽  
Serum Samples ◽  
Serum Mirna ◽  
Diagnosis And Prognosis ◽  
Mirna Expression Profiling

The aim of this study was to explore the predictive value of serum micro-RNA (miRNA)-205 in the diagnosis and prognosis of prostate cancer, and analyze miRNA-205 target genes and functions. Eight patients diagnosed with prostate cancer or benign prostatic hyperplasia (BPH) that were treated in January 2011 were selected. The serum samples between the two groups were analyzed for miRNA expression profiling, and the differentially expressed miRNA-205 was selected for further analysis. The serum samples of 64 patients with prostate cancer and 20 patients with BPH from March 2011 to March 2013 were collected for qPCR verification. We evaluated the correlation between miRNA-205 expression level and clinicopathological data of 64 patients with prostate cancer and its prognostic value. Finally, through bioinformatic analysis, target genes of miRNA-205 were predicted, and gene ontology (GO) analysis and signal pathway analysis were performed. A total of 657 differential miRNAs were screened from miRNA expression profiling. Compared with patients with BPH, miRNA-205 showed lower expression in the serum of patients with prostate cancer. Serum miRNA-205 + PSA combined had the strongest predictive ability, 0.805. The expression level of miRNA-205 in the patients with a Gleason score ≥7 was lower than that in patients with a Gleason score <7, Low miRNA-205 expression was associated with bone metastasis and higher T stage ratings, and the 5-year overall survival rate of the low miRNA-205 expression group was lower than the high miRNA-205 expression group. A total of 27 miRNA-205 target genes were predicted. The target genes of miRNA-205 are mainly enriched in biological functions such as cell adhesion and GTP kinase activity. The target genes of miRNA-205 are mainly enriched in Axon guidance and signal transduction by L1 and other signal pathways. In this study, serum miRNA-205 was successfully identified as a potential noninvasive serum marker for diagnosis and prognosis of prostate cancer, which will be helpful for future clinical research and prostate cancer drug target design.

scholarly journals Capturing large genomic contexts for accurately predicting enhancer-promoter interactions

2021 ◽  
Author(s):  
Ken Chen ◽  
Huiying Zhao ◽  
Yuedong Yang
Keyword(s):  
Target Gene ◽  
Target Genes ◽  
Cell Types ◽  
Training Data ◽  
Independent Test ◽  
Distant Target ◽  
Comparable Performance ◽  
Precision Recall Curve ◽  
Different Cell Types ◽  
The Impact

AbstractAccurately identifying enhancer-promoter interactions (EPIs) is challenging because enhancers usually act on the promoters of distant target genes. Although a variety of machine learning and deep learning models have been developed, many of them are not designed to or could not be well applied to predict EPIs in cell types different from the training data. In this study, we develop the TransEPI model for EPI prediction based on datasets derived from Hi-C and ChIA-PET data. TransEPI compiles genomic features from large intervals harboring the enhancer-promoter pair and adopts a Transformer-based architecture to capture the long-range dependencies. Thus, TransEPI could achieve more accurate prediction by addressing the impact of other genomic loci that may competitively interact with the enhancer-promoter pair. We evaluate TransEPI in a challenging scenario, where the independent test samples are predicted by models trained on the data from different cell types and chromosomes. TransEPI robustly predicts cross-cell-type EPI prediction by achieving comparable performance in cross-validation and independent test. More importantly, TransEPI significantly outperforms the state-of-the-art EPI models on the independent test datasets, with the Area Under Precision-Recall Curve (auPRC) score increasing by 48.84 % on average. Hence, TransEPI is applicable for accurate EPI prediction in cell types without chromatin structure data. Moreover, we find the TransEPI framework could also be extended to identify the target gene of non-coding mutations, which may facilitate studying pathogenic non-coding mutations.

scholarly journals The effects of long non-coding ribonucleic acids on various cellular components in rheumatoid arthritis

Rheumatology ◽  
2019 ◽  
Vol 59 (1) ◽  
pp. 46-56 ◽  
Author(s):  
Yilong Fang ◽  
Jiajie Tu ◽  
Dafei Han ◽  
Yawei Guo ◽  
Wenming Hong ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Autoimmune Diseases ◽  
Cell Types ◽  
Review Article ◽  
Diagnosis And Treatment ◽  
Ribonucleic Acids ◽  
Non Coding Rnas ◽  
Different Cell Types ◽  
Cellular Components

Abstract RA is a chronic, autoimmune-mediated inflammatory pathology. Long non-coding RNAs (lncRNAs) are a novel group of non-coding RNAs with a length of &gt;200 nucleotides. There are reports emerging that suggest that lncRNAs participate in establishing and sustaining autoimmune diseases, including RA. In this review article, we highlight the functions of lncRNAs in different cell types in RA. Our review indicates that lncRNAs affect various cellular components and are novel candidates that could constitute promising targets for the diagnosis and treatment of RA.

scholarly journals Specific Regulatory Motifs Predict Glucocorticoid Responsiveness of Hippocampal Gene Expression

Endocrinology ◽  
2011 ◽  
Vol 152 (10) ◽  
pp. 3749-3757 ◽  
Author(s):  
N. A. Datson ◽  
J. A. E. Polman ◽  
R. T. de Jonge ◽  
P. T. M. van Boheemen ◽  
E. M. T. van Maanen ◽  
...  
Keyword(s):  
Target Genes ◽  
Zinc Finger Protein ◽  
Cell Types ◽  
Nucleotide Composition ◽  
Rat Hippocampus ◽  
Glucocorticoid Response ◽  
Direct Binding ◽  
Flanking Sequences ◽  
Different Cell Types ◽  
High Degree

The glucocorticoid receptor (GR) is an ubiquitously expressed ligand-activated transcription factor that mediates effects of cortisol in relation to adaptation to stress. In the brain, GR affects the hippocampus to modulate memory processes through direct binding to glucocorticoid response elements (GREs) in the DNA. However, its effects are to a high degree cell specific, and its target genes in different cell types as well as the mechanisms conferring this specificity are largely unknown. To gain insight in hippocampal GR signaling, we characterized to which GRE GR binds in the rat hippocampus. Using a position-specific scoring matrix, we identified evolutionary-conserved putative GREs from a microarray based set of hippocampal target genes. Using chromatin immunoprecipitation, we were able to confirm GR binding to 15 out of a selection of 32 predicted sites (47%). The majority of these 15 GREs are previously undescribed and thus represent novel GREs that bind GR and therefore may be functional in the rat hippocampus. GRE nucleotide composition was not predictive for binding of GR to a GRE. A search for conserved flanking sequences that may predict GR-GRE interaction resulted in the identification of GC-box associated motifs, such as Myc-associated zinc finger protein 1, within 2 kb of GREs with GR binding in the hippocampus. This enrichment was not present around nonbinding GRE sequences nor around proven GR-binding sites from a mesenchymal stem-like cell dataset that we analyzed. GC-binding transcription factors therefore may be unique partners for DNA-bound GR and may in part explain cell-specific transcriptional regulation by glucocorticoids in the context of the hippocampus.

scholarly journals The Role of MicroRNAs in Regulatory T Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Chao Liu ◽  
Nannan Li ◽  
Guijian Liu
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Immune Responses ◽  
Small Rnas ◽  
Target Genes ◽  
Cell Types ◽  
Immune Disorders ◽  
Ongoing Research ◽  
Different Cell Types

MicroRNAs are a class of conserved, 20 nt-23 nt long, noncoding small RNAs that inhibit expression of their respective target genes in different cell types. Regulatory T cells (Tregs) are a subpopulation of T cells that negatively regulate immune responses, which is essential to immune homeostasis. Recent studies have indicated that microRNAs play an important role in the proliferation, differentiation, and functions of Treg. Here, we review the recent progress in understanding the roles of microRNAs in Treg and their dysregulation in immune-related diseases. This ongoing research continues to expand the understanding of Treg regulation and the mechanisms of immune disorders.

scholarly journals Sulphur starvation induces the expression of microRNA-395 and one of its target genes but in different cell types

2009 ◽  
Vol 57 (2) ◽  
pp. 313-321 ◽  
Author(s):  
Cintia Goulart Kawashima ◽  
Naoko Yoshimoto ◽  
Akiko Maruyama-Nakashita ◽  
Yumiko N. Tsuchiya ◽  
Kazuki Saito ◽  
...  
Keyword(s):  
Target Genes ◽  
Cell Types ◽  
Different Cell Types

scholarly journals Unveiling the ups and downs of miR-205 in physiology and cancer: transcriptional and post-transcriptional mechanisms

2020 ◽  
Vol 11 (11) ◽  
Author(s):  
Elena Ferrari ◽  
Paolo Gandellini
Keyword(s):  
Epithelial Cell ◽  
Target Genes ◽  
Cell Function ◽  
Cell Types ◽  
Future Application ◽  
Transcriptional Level ◽  
Aberrant Expression ◽  
Specific Tumor ◽  
And Function ◽  
Different Cell Types

Abstract miR-205 plays important roles in the physiology of epithelia by regulating a variety of pathways that govern differentiation and morphogenesis. Its aberrant expression is frequently found in human cancers, where it was reported to act either as tumor-suppressor or oncogene depending on the specific tumor context and target genes. miR-205 expression and function in different cell types or processes are the result of the complex balance among transcription, processing and stability of the microRNA. In this review, we summarize the principal mechanisms that regulate miR-205 expression at the transcriptional and post-transcriptional level, with particular focus on the transcriptional relationship with its host gene. Elucidating the mechanisms and factors regulating miR-205 expression in different biological contexts represents a fundamental step for a better understanding of the contribution of such pivotal microRNA to epithelial cell function in physiology and disease, and for the development of modulation strategies for future application in cancer therapy.

Sign in / Sign up

Export Citation Format

Share Document