Upregulated MicroRNA-155 Expression in Peripheral Blood Mononuclear Cells and Fibroblast-Like Synoviocytes in Rheumatoid Arthritis

Long, Li; Yu, Ping; Li, Yanying; Wang, Shiyao; Li, Ru; Shi, Jinxia; Zhang, Xiaoping; Li, Yanmei; Sun, Xiaolin; Zhou, Bin; Cui, Liufu; Li, Zhanguo

doi:10.1155/2013/296139

Cited by 90 publications

(89 citation statements)

References 18 publications

(21 reference statements)

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“…Ectopic miRNA-155 overexpression or inhibition did not clearly elucidate the mechanism underlying miR-155 mediated IKKe repression. 45,46 Interestingly, by transfecting LPS-activated macrophages with antagomir-155 we could effectively reduce mature miR-155 expression and observed significantly elevated CASP-3 mRNA (Fig. 6).…”

Section: Discussionmentioning

confidence: 93%

miR-155 targets Caspase-3 mRNA in activated macrophages

et al. 2015

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To secure the functionality of activated macrophages in the innate immune response, efficient life span control is required. Recognition of bacterial lipopolysaccharides (LPS) by toll-like receptor 4 (TLR4) induces downstream signaling pathways, which merge to induce the expression of cytokine genes and anti-apoptotic genes. MicroRNAs (miRNAs) have emerged as important inflammatory response modulators, but information about their functional impact on apoptosis is scarce. To identify miRNAs differentially expressed in response to LPS, cDNA libraries from untreated and LPSactivated murine macrophages were analyzed by deep sequencing and regulated miRNA expression was verified by Northern blotting and qPCR. Employing TargetScan TM we identified CASPASE-3 (CASP-3) mRNA that encodes a key player in apoptosis as potential target of LPSinduced miR-155. LPS-dependent primary macrophage activation revealed TLR4-mediated enhancement of miR-155 expression and CASP-3 mRNA reduction. Endogenous CASP-3 and cleaved CASP-3 protein declined in LPS-activated macrophages. Accumulation of miR-155 and CASP-3 mRNA in miRNA-induced silencing complexes (miRISC) was demonstrated by ARGONAUTE 2 (AGO2) immunoprecipitation. Importantly, specific antagomir transfection effectively reduced mature miR-155 and resulted in significantly elevated CASP-3 mRNA levels in activated macrophages. In vitro translation assays demonstrated that the target site in the CASP-3 mRNA 3'UTR mediates miR-155-dependent Luciferase reporter mRNA destabilization. Strikingly, Annexin V staining of macrophages transfected with antagomir-155 and stimulated with LPS prior to staurosporine (SSP) treatment implied that LPS-induced miR-155 prevents apoptosis through CASP-3 mRNA down-regulation. In conclusion, we report that miR-155-mediated CASP-3 mRNA destabilization in LPS-activated RAW 264.7 macrophages suppresses apoptosis, as a prerequisite to maintain their crucial function in inflammation.

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Section: Discussionmentioning

confidence: 93%

miR-155 targets Caspase-3 mRNA in activated macrophages

et al. 2015

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“…Meanwhile, it could not explain JIA with normal TNF-α and bad efficacy of TNF-α antagonist Effect of miR-19a and miR-21 on the JAK/STAT signaling pathway in the peripheral blood mononuclear cells of patients with systemic juvenile idiopathic arthritis to systematic arthritis, thus it was assumed that there was an interaction of a different signaling pathway in JIA. Despite recent random control studies suggesting that there are various expression levels of numerous types of miRNA, including miR-155, miR-19a, miR-203, miR-21 and miR-124a, in synovioblasts, PBMC and T cells from patients with RA (7)(8)(9)(10)(11)(12)(13)(14), the studies did not investigate the target genes of miRNAs, which could demonstrate the immunological dysregulation, inflammation and differentiation of cells. Therefore, in the present study, miR-19a, miR-21 and their associated target genes involved in SJIA were used to investigate the roles of miRNA in SJIA.…”

Section: Introductionmentioning

confidence: 99%

Effect of miR-19a and miR-21 on the JAK/STAT signaling pathway in the peripheral blood mononuclear cells of patients with systemic juvenile idiopathic arthritis

Xie

et al. 2016

Experimental and Therapeutic Medicine

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Abstract.Overexpression of the components of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway are key factors of the pathogenic mechanisms underlying systematic juvenile idiopathic arthritis (SJIA). The present study aimed to investigate the association between microRNA (miR)-19a, miR-21 and the JAK/STAT signaling pathway. A total of 20 patients with SJIA were included in the study, and peripheral blood mononuclear cells (PBMCs) from 20 normal controls were also collected. RNAiso was used to extract total RNA, and the RNA was then reverse transcribed into cDNA. Primers were designed to detect the mRNA of miR-19a and miR-21, and U6 was set as the internal parameter. In addition, the mRNA of STAT3, suppressor of cytokine signaling 3 (SOCS3), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) was detected, and β-actin was set as the internal parameter. Reverse transcription-quantitative polymerase chain reaction was performed to detect the expression levels of these proteins in patients with SJIA and control subjects, and non-parametric tests were used to analyze the statistical differences in 2 -ΔΔCq between the two groups. The expression levels of miR-19a and miR-21 were significantly lower in the SJIA group compared with the control group (P<0.05). SOCS3, TNF-α and STAT3 were shown to be the target genes of miR-19a and miR-21, as determined by Targetscan. The expression levels of STAT3, SOCS3, TNF-α and IL-6 mRNA were significantly higher compared with those of the control group (P<0.05). In the PBMCs of sthe patients with SJIA, miR-19a and miR-21 expression levels were lower compared with those of the control group, and the JAK/STAT signaling pathway was activated, which indicated that miR-19a and miR-21 may participate in the activation of the JAK/STAT signaling pathway.

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“…For instance, Li Z's research suggested that miR-155 overexpressed in RAFLSs decreased MMP-3 levels and inhibited the proliferation and invasion of RAFLSs [31]. Ogando J et al demonstrated that Notch signaling pathway is inhibited by the overexpression of miR-223 in RA patients [32].…”

Section: Discussionmentioning

confidence: 99%

miR-338-5p Regulates the Viability, Proliferation, Apoptosis and Migration of Rheumatoid Arthritis Fibroblast-Like Synoviocytes by Targeting NFAT5

Guo¹,

Ding²,

Jiang³

et al. 2018

Cell Physiol Biochem

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Background/Aims: MicroRNAs (miRNAs) have been reported to be involved in Rheumatoid arthritis (RA) pathogenesis and prognosis. However, little is known about the disease mechanism in RA. Here, we aim to investigate the potential association between miR-338-5p and NFAT5 in RA. Methods: Aberrant expression of miR-338-5p in RA tissues and rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs) compared to the normal were determined by RT-qPCR. Cell viability was determined using the CCK-8 assay, and cell apoptosis was analyzed via Annexin V-FITC/PI double staining and was detected using flow cytometry. The targeted relationship was determined by TargetScan database and dual luciferase reporter gene assay. Results: Upregulation of miR-338-5p facilitated the proliferation, migration, invasion and induced G0/G1 arrest of RAFLSs while miR-338-5p inhibitor functioned oppositely. Nuclear factor of activated T-cells 5 (NFAT5) was confirmed as a downstream target of miR-338-5p which expression was directly suppressed by miR-338-5p. Overexpression of NFAT5 attenuated the proliferation and metastasis of RAFLSs and those changes could be rescued by co-transfection of miR-338-5p. Conclusion: miR-338-5p promotes RAFLS’s viability and proliferation, migration by targeting NFAT5, suggesting a novel therapeutic strategy for RA.

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Upregulated MicroRNA-155 Expression in Peripheral Blood Mononuclear Cells and Fibroblast-Like Synoviocytes in Rheumatoid Arthritis

Cited by 90 publications

References 18 publications

miR-155 targets Caspase-3 mRNA in activated macrophages

miR-155 targets Caspase-3 mRNA in activated macrophages

Effect of miR-19a and miR-21 on the JAK/STAT signaling pathway in the peripheral blood mononuclear cells of patients with systemic juvenile idiopathic arthritis

miR-338-5p Regulates the Viability, Proliferation, Apoptosis and Migration of Rheumatoid Arthritis Fibroblast-Like Synoviocytes by Targeting NFAT5

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