Dysregulation of microRNAs in autoimmune diseases: Pathogenesis, biomarkers and potential therapeutic targets

Cancer Letters, Год журнала: 2018, Номер 428, С. 90 - 103

Опубликована: Апрель 20, 2018

Язык: Английский

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Cytokine Targeting by miRNAs in Autoimmune Diseases

Frontiers in Immunology, Год журнала: 2019, Номер 10

Опубликована: Янв. 28, 2019

Persistent and excessive cytokine production is a hallmark of autoimmune disease that may play role in pathogenesis amplification. Therefore, neutralization useful therapeutic strategy to treat immune-mediated conditions. MicroRNAs (miRNAs) are small non-coding RNA molecules regulate gene expression diverse biological processes. Altered miRNA levels observed most diseases recognized influence autoimmunity through different mechanisms. Here, we review the impact altered on cytokines relevant pathogenic autoimmunity, namely primary pro-inflammatory cytokines, IL-17/IL-23 axis, type I interferons IL-10. Regulation can be either "direct" target cytokine, or "indirect", meaning one given post-trascriptionally regulates protein turn influences level cytokine. In addition, miRNAs associated with extracellular vesicles neighbouring cells, post-transcriptionally via stimulation innate immune RNA-sensors, such as Toll-like receptors. Because their tremendous potential physiological pathological regulators, limelight promising future biopharmaceuticals. Thus, these studies lead near design testing next generation drugs autoimmunity.

Язык: Английский

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DNRLMF-MDA:Predicting microRNA-Disease Associations Based on Similarities of microRNAs and Diseases

IEEE/ACM Transactions on Computational Biology and Bioinformatics, Год журнала: 2017, Номер 16(1), С. 233 - 243

Опубликована: Ноя. 22, 2017

MicroRNAs (miRNAs) are a class of non-coding RNAs about $\sim$ 22nt nucleotides. Studies have proven that miRNAs play key roles in many human complex diseases. Therefore, discovering miRNA-disease associations is beneficial to understanding disease mechanisms, developing drugs, and treating It well known it time-consuming expensive process discover the via biological experiments. Alternatively, computational models could provide low-cost high-efficiency way for predicting associations. In this study, we propose method (called DNRLMF-MDA) predict based on dynamic neighborhood regularized logistic matrix factorization. DNRLMF-MDA integrates associations, functional similarity Gaussian Interaction Profile (GIP) kernel miRNAs, GIP Especially, positive observations (known associations) assigned higher importance levels than negative (unknown associations).DNRLMF-MDA computes probability miRNA would interact with by factorization method, where latent vectors diseases represent properties diseases, respectively, further improve prediction performance regularized. The 5-fold cross validation adopted assess our DNRLMF-MDA, as other competing methods comparison. experiments show outperforms state-of-art PBMDA. AUC values three datasets 0.9357, 0.9411, 0.9416, which superior PBMDA's results 0.9218, 0.9187, 0.9262. average computation times per 38, 46, 50 seconds, shorter 10869, 916, 8448 respectively. also can potential new miRNAs. Furthermore, case studies illustrate an effective

Язык: Английский

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The Involvement of MicroRNAs in Modulation of Innate and Adaptive Immunity in Systemic Lupus Erythematosus and Lupus Nephritis

Journal of Immunology Research, Год журнала: 2018, Номер 2018, С. 1 - 15

Опубликована: Янв. 1, 2018

Noncoding RNAs (ncRNAs), including microRNAs (miRNAs), represent a family of RNA molecules that do not translate into protein. Nevertheless, they have the ability to regulate gene expression and play an essential role in immune cell differentiation function. MicroRNAs were found be differentially expressed various tissues, changes their been associated with several pathological processes. Yet, roles systemic lupus erythematosus (SLE) nephritis (LN) remain elucidated. Both SLE LN are characterized by complex dysfunction innate adaptive immunity. Recently, significant findings made understanding through use genetic variant identification pattern analysis mouse models, as well epigenetic analyses. Abnormalities responses, cytokine chemokine production, activation, apoptosis linked unique number miRNAs implicated pathogenesis this autoimmune disease. The recent evidence significantly increased drives renewed interest efficient therapy targets. This review aims at providing overview current state research on LN.

Язык: Английский

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An update on the role of type I interferons in systemic lupus erythematosus and Sjögren's syndrome

Current Opinion in Rheumatology, Год журнала: 2018, Номер 30(5), С. 471 - 481

Опубликована: Июнь 10, 2018

Systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS) share several clinical laboratory features, including an overexpression of type I interferon (IFN) regulated genes. The genetic background to this IFN signature the role system in disease process have been partly clarified. Here, we summarize latest information concerning both diseases.A number gene variants signalling pathways associate with increased risk for SLE pSS ethnicities. function some has elucidated, as well importance epigenetic changes MicroRNA-451 miR-302d shown target regulatory factor 8 9, suggesting that noncoding RNAs can control system. A prominent activation is related manifestations, a more severe phenotype. Phase II studies suggest beneficial effects blocking receptor.The activated strong component, important etiopathogenesis be targeted.

Язык: Английский

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MicroRNAs as prognostic biomarkers for (cancer–associated) venous thromboembolism

Journal of Thrombosis and Haemostasis, Год журнала: 2023, Номер 21(1), С. 7 - 17

Опубликована: Янв. 1, 2023

MicroRNAs (miRNAs) are small noncoding RNAs with gene regulatory functions and commonly dysregulated in disease states. As miRNAs relatively stable, easily measured, accessible from plasma or other body fluids, they promising biomarkers for the diagnosis prediction of cancer cardiovascular diseases. Venous thromboembolism (VTE) is third most common worldwide high morbidity mortality. The suggested roles regulating pathophysiology VTE as nowadays more evidenced. Patients at increased risk developing compared to general population. However, current models cancer–associated thrombosis (CAT) perform suboptimally, novel therefore urgently needed identify which patients may benefit thromboprophylaxis. This review will first discuss how mechanistically contribute VTE. Next, potential use predictive subjects without reviewed, followed by an in-depth focus on CAT. Several identified CAT were found be differentially regulated well, giving clues We propose that subsequent studies should adequately sized determine panel best predicts Thereafter, validation using comparable patient populations required ultimately unveil whether miRNAs—as standalone incorporated into existing models—are valuable biomarkers.

Язык: Английский

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IMMUNOINFLAMMATORY RHEUMATIC DISEASES ASSOCIATED WITH TYPE I INTERFERON: NEW EVIDENCE

Rheumatology Science and Practice, Год журнала: 2019, Номер 57(4), С. 452 - 461

Опубликована: Сен. 16, 2019

Immunoinflammatory rheumatic diseases (IIRDs) are a large group of pathological conditions with impaired immunological tolerance to autogenous tissues, leading inflammation and irreversible organ damage. The review discusses current ideas on the role type I interferons in immunopathogenesis IIRDs, primarily systemic lupus erythematosus, new possibilities for personalized therapy.

Язык: Английский

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Extracellular Vesicles Derived From Lipopolysaccharide‐Challenged Gingival Fibroblast Reveal Distinct miRNA Expression Patterns Associated With Reduced Cancer Survival

Clinical and Experimental Dental Research, Год журнала: 2025, Номер 11(1)

Опубликована: Фев. 1, 2025

ABSTRACT Objectives Periodontitis is a prevalent inflammatory disease with established systemic implications. Extracellular vesicles (EVs) have emerged as key mediators of intercellular communication, potentially linking periodontitis to diseases. However, the molecular cargo EVs from inflamed periodontal cells remains poorly characterized. This study investigates EV human gingival fibroblasts (hGF‐hTERT) following lipopolysaccharide (LPS) stimulation and explores their potential role in cancer progression. Materials Methods were isolated LPS‐treated untreated via ultracentrifugation. Dynamic light scattering scanning electron microscopy characterized size morphology. RNA sequencing identified differentially expressed miRNAs, validated by qPCR. Functional pathway enrichment in‐silico analyses using The Cancer Genome Atlas (TCGA) performed assess EV‐associated miRNA impact on tumorigenesis. Results concentration remained unchanged after LPS stimulation. LPS‐derived exhibited 2.6‐fold increase content, three significantly upregulated miRNAs: miR‐146a‐5p, miR‐486‐5p, miR‐451a. analysis revealed involvement inflammation, immune modulation, pathways. In vitro, enhanced prostate (LnCap) cell proliferation. TCGA linked miRNAs poor prognosis. Conclusions alters fibroblast‐derived EVs, enhancing pathways associated inflammation These findings suggest mechanistic for pathogenesis, warranting further investigation into diagnostic therapeutic potential.

Язык: Английский

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Exploring the Role of Non-Coding RNAs in the Pathophysiology of Systemic Lupus Erythematosus

Biomolecules, Год журнала: 2020, Номер 10(6), С. 937 - 937

Опубликована: Июнь 22, 2020

Systemic lupus erythematosus (SLE) is a chronic immune-related disorder designated by lack of tolerance to self-antigens and the over-secretion autoantibodies against several cellular compartments. Although exact pathophysiology SLE has not been clarified yet, this strong genetic component based on results familial aggregation twin studies. Variation in expression non-coding RNAs shown influence both susceptibility clinical course disorder. Several long (lncRNAs) such as GAS5, MALAT1 NEAT1 are dysregulated patients. Moreover, variants within lncRNAs SLEAR linc00513 have associated with risk The dysregulation number peripheral blood patients potentiated them biomarkers for diagnosis, disease activity therapeutic response. MicroRNAs (miRNAs) also affect apoptosis function immune cells. Taken together, there compelling rationale better understanding involvement these two classes pathogenesis SLE. Clarification transcripts potential elucidate molecular provide new opportunities development targeted therapies

Язык: Английский

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miRNA-Mediated Control of B Cell Responses in Immunity and SLE

Frontiers in Immunology, Год журнала: 2021, Номер 12

Опубликована: Май 17, 2021

Loss of B cell tolerance is central to autoimmune diseases such as systemic lupus erythematosus (SLE). As such, the mechanisms involved in development, maturation, activation, and function that are aberrantly regulated SLE interest design targeted therapeutics. While many factors generation regulation responses, miRNAs have emerged critical regulators these responses within last decade. To date, miRNA involvement has largely been studied non-autoimmune, immunization-based systems. However, profiles also strongly associated with human patients molecules proven both promotion disease mouse models formation autoreactive responses. Functionally, small non-coding RNAs bind complementary sequences located target mRNA transcripts mediate transcript degradation or translational repression, invoking a post-transcriptional level genetic regulation. Due their capacity diverse range pathways different immune types throughout various stages development response, targeting an interesting potential therapeutic avenue. Herein, we focus on what currently known about normal primarily highlighting confirmed functions models. We discuss areas should be addressed future studies whether miRNA-centric therapeutics may viable alternative for treatment SLE.

Язык: Английский

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