The Roles of Noncoding RNAs in Systemic Sclerosis

Liu, Yongmei; Cheng, Linlin; Zhan, Haoting; Li, Haolong; Li, Xiaomeng; Huang, Yuan; Li, Yongzhe

doi:10.3389/fimmu.2022.856036

Cited by 7 publications

(6 citation statements)

References 121 publications

(118 reference statements)

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“…The higher amount of ENG observed also in SSc fibroblasts seems to be more pronounced at the protein, rather than mRNA, level and the suggestion is that post-transcriptional mechanisms could enhance protein expression in SSc fibroblasts ( 43 ). Our search did not provide any result regarding either this process, or an altered expression of miRNAs in SSc regulating ENG ( 63 ), making this an interesting field of future investigation.…”

Section: Discussionmentioning

confidence: 91%

Endoglin and Systemic Sclerosis: A PRISMA-driven systematic review

et al. 2022

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BackgroundSystemic Sclerosis (SSc) is a rare autoimmune disease whose pathogenesis is still poorly understood. The Transforming Growth Factor β superfamily is considered pivotal and a crucial role has been suggested for the type III receptor, Endoglin (ENG). The aim of this systematic review is to investigate and combine the current clinical and molecular available data, to suggest novel hints for further studies.MethodsWe followed PRISMA guidelines; the search was performed on three databases (MEDLINE, Web of Science, Embase) in date November 2nd, 2021. Subsequent to the exclusion of duplicates, we applied as inclusion criteria: 1. focus on the relationship between ENG and SSc; 2. English language. As exclusion criteria: 1. ENG exclusively as a cellular biomarker; 2. no focus on ENG-SSc relationship; 3. review articles and 4. abstracts that did not add novel data. Eligibility was assessed independently by each author to reduce biases. We divided records into clinical and molecular works and subgrouped them by their study features and aim.ResultsWe selected 25 original papers and 10 conference abstracts. Molecular studies included 6 articles and 4 abstracts, whereas clinical studies included 17 articles and 6 abstracts; 2 articles presented both characteristics. Molecular studies were focussed on ENG expression in different cell types, showing an altered ENG expression in SSc-affected cells. Clinical studies mainly suggested that different disease phenotypes can be related to peculiar disregulations in soluble ENG concentrations.DiscussionConcerning the possible limits of our search, boolean operators in our strings might have been uneffective. However, the use of different strings in different databases should have reduced this issue at a minimum. Another bias can be represented by the selection step, in which we excluded many articles based on the role of Endoglin as a histological vascular marker rather than a signaling receptor. We tried to reduce this risk by performing the selection independently by each author and discussing disagreements. Our systematic review pointed out that ENG has a pivotal role in activating different TGFβ-stimulated pathways that can be crucial in SSc pathogenesis and progression.

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Section: Discussionmentioning

confidence: 91%

Endoglin and Systemic Sclerosis: A PRISMA-driven systematic review

et al. 2022

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“…Increasing studies have investigated non-invasive biomarkers to diagnose, evaluate, and treat SSc; however, few of these biomarkers are used clinically ( 8 ). Compared to circulating non-coding RNAs in the serum or plasma, the abnormal expression of non-coding RNAs carried by cirexos in SSc have the advantages of stability and practicability as novel biomarkers and therapeutic targets for the diagnosis and treatment of SSc ( 13 , 74 , 75 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of lncRNA–miRNA–mRNA networks in circulating exosomes as potential biomarkers for systemic sclerosis

et al. 2023

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ObjectiveThis study aimed to analyze potential biomarkers for systemic sclerosis (SSc) by constructing lncRNA–miRNA–mRNA networks in circulating exosomes (cirexos).Materials and methodsDifferentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs) in SSc cirexos were screened using high-throughput sequencing and detected with real-time quantitative PCR (RT-qPCR). Differentially expressed genes (DEGs) were analyzed using the DisGeNET, GeneCards, GSEA4.2.3, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Receiver operating characteristic (ROC) curves, correlation analyses, and a double-luciferase reporter gene detection assay were used to analyze competing endogenous RNA (ceRNA) networks and clinical data.ResultsIn this study, 286 DEmRNAs and 192 DElncRNAs were screened, of which 18 DEGs were the same as the SSc-related genes. The main SSc-related pathways included extracellular matrix (ECM) receptor interaction, local adhesion, platelet activation, and IgA production by the intestinal immune network. A hub gene, COL1A1, was obtained by a protein–protein interaction (PPI) network. Four ceRNA networks were predicted through Cytoscape. The relative expression levels of COL1A1, ENST0000313807, and NON-HSAT194388.1 were significantly higher in SSc, while the relative expression levels of hsa-miR-29a-3p, hsa-miR-29b-3p, and hsa-miR-29c-3p were significantly lower in SSc (P < 0.05). The ROC curve showed that the ENST00000313807-hsa-miR-29a-3p-COL1A1 network as a combined biomarker of SSc is more valuable than independent diagnosis, and that it is correlated with high-resolution CT (HRCT), Scl-70, C-reactive protein (CRP), Ro-52, IL-10, IgM, lymphocyte percentage, neutrophil percentage, albumin divided by globulin, urea, and RDW-SD (P < 0.05). Double-luciferase reporter gene detection showed that ENST00000313807 interacts with hsa-miR-29a-3p, which interacts with COL1A1.ConclusionThe ENST00000313807-hsa-miR-29a-3p-COL1A1 network in plasma cirexos represents a potential combined biomarker for the clinical diagnosis and treatment of SSc.

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“…While classical TGF-β pathway signaling is mediated by the binding of TGF-β1 to transforming growth factor beta receptors II (TGFBR2) ( Huang et al, 2022 ), which subsequently phosphorylates and activates the Smad2 and Smad3, thereby promoting myofibroblast proliferation and migration, and leading to cardiac fibrosis ( Zhang et al, 2022a ). Non-coding RNAs (ncRNAs) can be broadly classified into microRNAs (miRNAs), long-stranded non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) according to their functions ( Iu et al, 2022 ). The ncRNAs can bind to multiple molecular targets, and form regulatory networks in many biological activities, including initiation of specific cellular biological responses, regulation of gene expression, intracellular signaling, and epigenetic genetic modifications ( Statello et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Mechanism of action of non-coding RNAs and traditional Chinese medicine in myocardial fibrosis: Focus on the TGF-β/Smad signaling pathway

Meng²,

Wang³

et al. 2023

Front. Pharmacol.

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Cardiac fibrosis is a serious public health problem worldwide that is closely linked to progression of many cardiovascular diseases (CVDs) and adversely affects both the disease process and clinical prognosis. Numerous studies have shown that the TGF-β/Smad signaling pathway plays a key role in the progression of cardiac fibrosis. Therefore, targeted inhibition of the TGF-β/Smad signaling pathway may be a therapeutic measure for cardiac fibrosis. Currently, as the investigation on non-coding RNAs (ncRNAs) move forward, a variety of ncRNAs targeting TGF-β and its downstream Smad proteins have attracted high attention. Besides, Traditional Chinese Medicine (TCM) has been widely used in treating the cardiac fibrosis. As more and more molecular mechanisms of natural products, herbal formulas, and proprietary Chinese medicines are revealed, TCM has been proven to act on cardiac fibrosis by modulating multiple targets and signaling pathways, especially the TGF-β/Smad. Therefore, this work summarizes the roles of TGF-β/Smad classical and non-classical signaling pathways in the cardiac fibrosis, and discusses the recent research advances in ncRNAs targeting the TGF-β/Smad signaling pathway and TCM against cardiac fibrosis. It is hoped, in this way, to give new insights into the prevention and treatment of cardiac fibrosis.

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The Roles of Noncoding RNAs in Systemic Sclerosis

Cited by 7 publications

References 121 publications

Endoglin and Systemic Sclerosis: A PRISMA-driven systematic review

Endoglin and Systemic Sclerosis: A PRISMA-driven systematic review

Identification of lncRNA–miRNA–mRNA networks in circulating exosomes as potential biomarkers for systemic sclerosis

Mechanism of action of non-coding RNAs and traditional Chinese medicine in myocardial fibrosis: Focus on the TGF-β/Smad signaling pathway

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