Serum miR‐224, miR‐760, miR‐483‐5p, miR‐378 and miR‐375 as potential novel biomarkers in rheumatoid arthritis

Abdelaleem, Omayma O; Fouad, Nermeen Ahmed; Shaker, Olfat; Ahmed, Tarek I.; Abdelghaffar, Noha K.; Eid, Hanaa M.; Mohamed, Abdelrahmaan A; Elebiary, Ahmed; Mohamed, Mohamed M.; Mahmoud, Rania H.

doi:10.1111/ijcp.14651

Cited by 6 publications

(3 citation statements)

References 43 publications

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“…This result suggests that miR-378a-5p may play a vital role in the pathogenesis of RA and function as a potential therapeutic target for RA. On the contrary, recent studies have shown a significant increase in the expression of miR-378a-5p in the serum of RA patients [ 62 ] and in the synovial tissue of patients with osteoarthritis who have undergone an extra-articular implant [ 63 ]. Furthermore, a high enrichment of miR-378a-5p was found in EVs derived from MSCs, which could contribute to the attenuation of colitis [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Bone Marrow Mesenchymal Stem Cells Release miR-378a-5p-Carried Extracellular Vesicles to Alleviate Rheumatoid Arthritis

Zhang,

Jiao,

Wang

2023

J Innate Immun

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This study investigates whether bone marrow mesenchymal stem cells (BMSCs)-derived extracellular vesicles (EVs) can affect rheumatoid arthritis (RA) by delivering microRNA (miR)-378a-5p to regulate the IRF1/STAT1 axis. We identified RA-associated miRNAs using GEO microarray dataset GSE121894. We found the most important miRNAs in RA synovial tissues using RT-qPCR. BMSCs-derived EVs were ultracentrifuged and co-cultured with HSMECs in vitro. Dual-luciferase and RIP studies examined miR-378a-5p's specific binding to IRF1. We also measured angiogenesis, migration, and proliferation using CCK-8, Transwell, and tube formation assays. CIA (collagen-induced arthritis) mice models were created by inducing arthritis and scoring it. RA synovial tissues had low miR-378a-5p expression, whereas BMSC-derived EVs had high levels. The transfer of miR-378a-5p by BMSC-derived EVs to HSMECs boosted proliferation, migration, and angiogenesis. miR-378a-5p inhibited IRF1. MiR-378a-5p-containing BMSC-derived EVs decreased STAT1 phosphorylation and HSMEC IRF1 expression. EVs with miR-378a-5p mimic promoted HSMEC proliferation, migration, and angiogenesis, whereas dexmedetomidine inhibited STAT1 phosphorylation. In CIA mice, BMSC-derived EVs containing miR-378a-5p enhanced synovial vascular remodeling and histopathology. Thus, miR-378a-5p from BMSC-derived EVs promotes HSMEC proliferation, migration, and angiogenesis, inactivating the IRF1/STAT1 axis and preventing rheumatoid arthritis.

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Section: Discussionmentioning

confidence: 99%

Bone Marrow Mesenchymal Stem Cells Release miR-378a-5p-Carried Extracellular Vesicles to Alleviate Rheumatoid Arthritis

Zhang,

Jiao,

Wang

2023

J Innate Immun

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“…miR-23b levels were found to be significantly elevated in the synovial tissue cells and plasma of RA patients and positively correlated with platelet (PLT) counts, CRP, hypersensitive-CRP (hs-CRP), ESR, and DAS28 ( p < 0.05), and treatment reversed the trend of elevated plasma miR-23b levels ( 107 ). Moreover, miR-23 could regulate CXCL12 through the NF-κB signaling pathway to suppress the inflammation involved in RA pathogenesis ( 108 ).…”

Section: Candidate Rnas As Biomarkers For Ramentioning

confidence: 99%

Biomarkers (mRNAs and non-coding RNAs) for the diagnosis and prognosis of rheumatoid arthritis

Jiang

Zhong

et al. 2023

Front. Immunol.

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In recent years, diagnostic and therapeutic approaches for rheumatoid arthritis (RA) have continued to improve. However, in the advanced stages of the disease, patients are unable to achieve long-term clinical remission and often suffer from systemic multi-organ damage and severe complications. Patients with RA usually have no overt clinical manifestations in the early stages, and by the time a definitive diagnosis is made, the disease is already at an advanced stage. RA is diagnosed clinically and with laboratory tests, including the blood markers C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) and the autoantibodies rheumatoid factor (RF) and anticitrullinated protein antibodies (ACPA). However, the presence of RF and ACPA autoantibodies is associated with aggravated disease, joint damage, and increased mortality, and these autoantibodies have low specificity and sensitivity. The etiology of RA is unknown, with the pathogenesis involving multiple factors and clinical heterogeneity. The early diagnosis, subtype classification, and prognosis of RA remain challenging, and studies to develop minimally invasive or non-invasive biomarkers in the form of biofluid biopsies are becoming more common. Non-coding RNA (ncRNA) molecules are composed of long non-coding RNAs, small nucleolar RNAs, microRNAs, and circular RNAs, which play an essential role in disease onset and progression and can be used in the early diagnosis and prognosis of RA. In this review of the diagnostic and prognostic approaches to RA disease, we provide an overview of the current knowledge on the subject, focusing on recent advances in mRNA–ncRNA as diagnostic and prognostic biomarkers from the biofluid to the tissue level.

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“…Concentration of circulating miR-23b , which positively correlates with ESR, CRP, and DAS-28, is significantly up-regulated after appropriate treatment, indicating that miR-23b is a dual marker for disease activity and prognosis ( 105 ). Similarly, miR-96-5p, miR-134-5p, miR-140-3p, miR-627-5p, miR-224, miR-760, miR-483-5p, miR-378, and miR-375 are not only diagnostic markers for RA, but also mirror disease activity ( 106 , 107 ). However, these studies are still descriptive.…”

Section: Blood and Serum-circulating Mirnas Provide Novel Opportuniti...mentioning

confidence: 99%

MicroRNA-Mediated Epigenetic Regulation of Rheumatoid Arthritis Susceptibility and Pathogenesis

Chang

Zhang

et al. 2022

Front. Immunol.

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MicroRNAs (miRNAs) play crucial roles in regulating the transcriptome and development of rheumatoid arthritis (RA). Currently, a comprehensive map illustrating how miRNAs regulate transcripts, pathways, immune system differentiation, and their interactions with terminal cells such as fibroblast-like synoviocytes (FLS), immune-cells, osteoblasts, and osteoclasts are still laking. In this review, we summarize the roles of miRNAs in the susceptibility, 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 NF-κB, Fas-FasL, JAK-STAT, and mTOR pathways. We outline how functional genetic variants of miR-499 and miR-146a partly explain susceptibility to RA. By regulating gene expression, miRNAs affect T cell differentiation into diverse cell types, including Th17 and Treg cells, thus constituting 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 opportunity to combine these miRNAs with antibodies to cyclic citrullinated peptide (ACCP) to allow accurate diagnosis and prognosis, particularly for seronegative patients. Furthermore, we review the evidence implicating miRNAs as promising biomarkers of efficiency and response of, and resistance to, disease-modifying anti-rheumatic drugs 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.

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Serum miR‐224, miR‐760, miR‐483‐5p, miR‐378 and miR‐375 as potential novel biomarkers in rheumatoid arthritis

Cited by 6 publications

References 43 publications

Bone Marrow Mesenchymal Stem Cells Release miR-378a-5p-Carried Extracellular Vesicles to Alleviate Rheumatoid Arthritis

Bone Marrow Mesenchymal Stem Cells Release miR-378a-5p-Carried Extracellular Vesicles to Alleviate Rheumatoid Arthritis

Biomarkers (mRNAs and non-coding RNAs) for the diagnosis and prognosis of rheumatoid arthritis

MicroRNA-Mediated Epigenetic Regulation of Rheumatoid Arthritis Susceptibility and Pathogenesis

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