Identification of a novel microRNA-141-3p/Forkhead box C1/β-catenin axis associated with rheumatoid arthritis synovial fibroblast function in vivo and in vitro

Wang, Jun; Wang, Yin; Zhang, Hui; Chang, Jun; Lu, Ming; Gao, Weilu; Li, Wendong; Li, Yetian; Li, Yin; Wang, Xiaohe; Wang, Yuejun; Gao, Mengru; Yin, Zhou

doi:10.7150/thno.45214

Cited by 30 publications

(24 citation statements)

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“…In this study, we found that FOXC1 was elevated in GC tissue and its level was associated with patients, poor prognosis. Furthermore, the results showed that FOXC1 can promote growth of GC by modulating the tumor cell cycle, as mediated by c-MYC and cyclin D1, further supporting the role of FOXC1 in GC progression (Wang et al, 2018(Wang et al, , 2020. c-Myc is a critical transcription factor, and its aberrant expression of c-Myc can promote tumorigenesis and development (Sansom et al, 2007).…”

Section: Discussionmentioning

confidence: 76%

FOXC1 Negatively Regulates DKK1 Expression to Promote Gastric Cancer Cell Proliferation Through Activation of Wnt Signaling Pathway

Jiang

Yao

et al. 2021

Front. Cell Dev. Biol.

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Gastric cancer (GC), characterized by uncontrolled growth, is a common malignant tumor of the digestive system. The Wnt signaling pathway plays an important role in the tumorigenesis and proliferation of GC. Many studies on this signaling pathway have focused on its intracellular regulatory mechanism, whereas little attention has been given to extracellular regulatory factors. Dickkopf-1 (Dkk1) is a secretory glycoprotein, and it can bind inhibit activation of the Wnt pathway. However, the regulation and mechanism of DKK1 in the proliferation of GC remain unclear. FOXC1 plays an important role in organ development and tumor growth, but its role in GC tumor growth remains unknown. In this study, we found that the FOXC1 is highly expressed in patients with GC and high expression of FOXC1 correlates to poor prognosis. In addition, we found that the Wnt signaling pathway in GC cells with high FOXC1 expression was strongly activated. FOXC1 negatively regulates DKK1 expression by binding to its promoter region, thereby promoting the activation of Wnt pathway. FOXC1 can also form a complex with unphosphorylated β-catenin protein in the cytoplasm and then dissociates from β-catenin in the nucleus, thereby promoting the entry of β-catenin into the nucleus and regulating expression of c-MYC, which promotes the proliferation of GC cells. Our study not only reveals the function and mechanism of FOXC1 in GC, but also provides a potential target for clinic GC treatment.

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Section: Discussionmentioning

confidence: 76%

FOXC1 Negatively Regulates DKK1 Expression to Promote Gastric Cancer Cell Proliferation Through Activation of Wnt Signaling Pathway

Jiang

Yao

et al. 2021

Front. Cell Dev. Biol.

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“…The RASFs were preserved, and other cells, such as infiltrating T cells and B cells, were removed following multiple passages. Many studies have used this protocol 19 , 20 . RASFs were cocultured with human Treg cells derived from in vitro amplification, and the induced Treg cells inhibited RASF proliferation and promoted apoptosis, suggesting that exogenous Treg cells inhibit the excessive activation of RASFs in RA pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…The cell number was calculated using a cell counter. This method has been used in many studies 19 , 20 .…”

Section: Methodsmentioning

confidence: 99%

Therapeutic Effect of Exogenous Regulatory T Cells on Collagen-induced Arthritis and Rheumatoid Arthritis

Wang

et al. 2020

Cell Transplant

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Regulatory T (Treg) cells have anti-inflammatory functions and heighten immune tolerance. The proportion and functions of Treg cells are perturbed in rheumatoid arthritis (RA), contributing to the excessive immune activation associated with this disease. We therefore hypothesized that supplementation with foreign Treg cells could be used to treat RA. To investigate the therapeutic effects of exogenous Treg cells on RA and its mechanism, we used human Treg cells to treat collagen-induced arthritis (CIA) in a rat model to observe whether exogenous Treg cells can treat the disease across species. Successful treatment would indicate that Treg cell transplantation in humans is more likely to affect RA. In the present study, human Treg cells were collected from healthy human peripheral blood and culture-expanded in vitro. Induced human Treg cells were injected into CIA rats via the tail vein. The rats’ lymphocyte subtypes, cytokines, and Th1/Th2 ratios were measured using flow cytometry. In the rats, following injection of the human Treg cells, the severity of CIA was significantly reduced ( P < 0.01), the proportion of endogenous Treg cells increased in the peripheral blood and spleen ( P = 0.007 and P < 0.01, respectively), and the proportion of B cells decreased ( P = 0.031). The IL-5 level, IL-6 level, and Th1/Th2 ratio in the peripheral blood were decreased ( P = 0.013, 0.009, and 0.012, respectively). The culture-expanded human Treg cells were also cultured with synovial fibroblast cells from RA patients (RASFs). After coculture with Treg cells, RASFs showed reduced proliferation ( P < 0.01) and increased apoptosis ( P = 0.037). These results suggest that exogenous and induced Treg cells can produce a therapeutic effect in RA and CIA by increasing endogenous Treg cells and RASF apoptosis and reducing B cells, the Th1/Th2 ratio, and secretion levels of IL-5 and IL-6. Treg cell transplantation could serve as a therapy for RA that does not cause immune rejection.

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“…As shown in Table 4, miRNA levels change various intracellular pathways, and the most prominent implicated pathways are those of NF-kB (192,198,207,212,213,222,229,230,238), PI3K/Akt (194,199,203,236), JAK/STAT (218, 219), TLR (208,220), b-catenin (215,217,235), and Wnt (223,235). In parallel, the efficacy of several miRNAs against RA has been verified in animal experiments.…”

Section: Epigenetic Targets For Treatment Of Rheumatoid Arthritismentioning

confidence: 90%

Promising Therapeutic Targets for Treatment of Rheumatoid Arthritis

et al. 2021

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Rheumatoid arthritis (RA) is a systemic poly-articular chronic autoimmune joint disease that mainly damages the hands and feet, which affects 0.5% to 1.0% of the population worldwide. With the sustained development of disease-modifying antirheumatic drugs (DMARDs), significant success has been achieved for preventing and relieving disease activity in RA patients. Unfortunately, some patients still show limited response to DMARDs, which puts forward new requirements for special targets and novel therapies. Understanding the pathogenetic roles of the various molecules in RA could facilitate discovery of potential therapeutic targets and approaches. In this review, both existing and emerging targets, including the proteins, small molecular metabolites, and epigenetic regulators related to RA, are discussed, with a focus on the mechanisms that result in inflammation and the development of new drugs for blocking the various modulators in RA.

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Identification of a novel microRNA-141-3p/Forkhead box C1/β-catenin axis associated with rheumatoid arthritis synovial fibroblast function in vivo and in vitro

Cited by 30 publications

References 0 publications

FOXC1 Negatively Regulates DKK1 Expression to Promote Gastric Cancer Cell Proliferation Through Activation of Wnt Signaling Pathway

FOXC1 Negatively Regulates DKK1 Expression to Promote Gastric Cancer Cell Proliferation Through Activation of Wnt Signaling Pathway

Therapeutic Effect of Exogenous Regulatory T Cells on Collagen-induced Arthritis and Rheumatoid Arthritis

Promising Therapeutic Targets for Treatment of Rheumatoid Arthritis

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