Regulation of NF-κB- and STAT1-mediated plasmacytoid dendritic cell functions by A20

Duy, Pham Ngoc; Thuy, Nguyen Thu; Trang, Bui Kieu; Giang, Nguyen Hoang; Vân, Nguyễn Thị Hồng; Xuân, Nguyễn Thị

doi:10.1371/journal.pone.0222697

Cited by 9 publications

(13 citation statements)

References 32 publications

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“…37 Moreover, some new strategies could suppress IκB activity via increasing IκB protein degradation. 38,39 Similarly, our results revealed that IκB was suppressed from transferring into the nucleus under the effect of nobiletin on BC cells.…”

Section: Discussionsupporting

confidence: 67%

Nobiletin promotes the pyroptosis of breast cancer via regulation of miR‐200b/JAZF1 axis

Wang¹,

Jian

Li³

et al. 2021

The Kaohsiung J of Med Scie

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Nobiletin is a polymethoxylated flavone present in citrus fruits, which has been reported to have inhibitory effects on tumorigenesis of cancers. However, the biological function of nobiletin in breast cancer (BC) is largely unknown. To investigate the effect of nobiletin on growth of BC cells, the cell viability of BC was measured by MTT assay. In addition, gene and protein expressions were detected by qRT-PCR and western blot, respectively. The apoptosis and pyroptosis of BC cells were tested by flow cytometry. Finally, the correlation between miR-200b and JAZF1 was detected by dual luciferase report. The data indicated that nobiletin inhibited the proliferation of BC cells in a dose-dependent manner. Moreover, miR-200b mimics-induced pyroptosis of BC cells was further increased by nobiletin. Meanwhile, JAZF1 was found to be the target of miR-200b. Moreover, nobiletin induced apoptosis and pyroptosis of BC cells via miR-200b/JAZF1/NF-κB axis. In conclusion, nobiletin inhibited the tumorigenesis of BC via regulation of miR-200b/JAZF1 axis. Thus, nobiletin might serve as a new agent for the treatment of BC.

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Section: Discussionsupporting

confidence: 67%

Nobiletin promotes the pyroptosis of breast cancer via regulation of miR‐200b/JAZF1 axis

Wang¹,

Jian

Li³

et al. 2021

The Kaohsiung J of Med Scie

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“…Although it is well known that A20 participates in inhibiting functional activation of several immune cells including dendritic, T and B cells (Duy et al, 2019;Hovelmeyer et al, 2011), the effect of A20 on PBMC function is not mentioned yet. In addition to the presence of dendritic, T and B cells, PBMCs also comprise of other cell types such as myeloid, NK cells and monocytes.…”

Section: Discussionmentioning

confidence: 99%

“…The cell migration is characterized by binding between chemokine receptors on the cell surface to specific ligands expressed on epithelial cells in lymphoid organs. A20 has been shown to inhibit the migration of cancer cells mediated through activation of NF-κB and signal transducer and activator of transcription (STAT) signalings (Chen et al, 2018;Duy et al, 2019). In order to maintain tissue homeostasis, the immune cells eventually undergo cell apoptosis, which is identified by activation of caspases and exposure of phosphatidylserine (PS) on the external leaflet of the plasma membrane.…”

Section: Introductionmentioning

confidence: 99%

The regulatory role of peripheral blood mononuclear cell function by A20

Xuân

Hoàng

2020

Vietnam J. Biotechnol.

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Peripheral blood mononuclear cells (PBMC) consist of lymphocytes (T cells, B cells, natural killer cells), monocytes and dendritic cells and play important roles in initiating and regulating immunity against pathogens or immunotolerance to allergens. Activation of PBMCs is induced upon exposure to multiple stimuli by the binding with toll-like receptors (TLRs), recognition elements of the innate immune system. A20 is a negative regulator of nuclear factor (NF)-κB-dependent immune reaction in response to TLR ligands. A20-deficient mice display severe inflammation, tissue damage in multiple organs, cachexia and premature mortality. Single nucleotide polymorphisms (SNPs) at A20 gene region in humans reduce the binding capacity of A20 to NF‐κB subunits, resulting in reduced expression and function of A20 and leading to the pathogenesis of autoimmune and cancers. Although the inhibitory role of A20 on immune cells including B, T and DC functions has been previously reported, the effect of A20 on PBMC function is not mentioned yet. The present study, therefore, explored whether A20 expression is involved in immunophenotypic changes, the release of cytokine production, cell migration, and apoptosis. To this end, immonophenotypic profile and cell apoptosis were examined by flow cytometry, secretion of inflammatory cytokines by ELISA and cell migration by a transwell migration assay. As a result, percentages of CD3+CD25+, CD19+CD25+, and CD11b+CD40+ expressing cells, the release of TNF-α and IL-1β and cell migration were enhanced in A20-silenced PBMCs. However, cell apoptosis was independent of the presence of A20 in PBMCs. In conclusion, these results attained in this study suggested that A20 expression might modulate the immune response in autoimmune disease and cancers.

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“…Lack of A20 or CYLD in mouse immune cells results in constitutive activity of several pathways, including nuclear factor kappalight-chain-enhancer of activated B cells (NF-κB) and signal transducer and activator of transcriptions (STATs). 6,7 In humans, inactivation of A20 leads to the progression of lymphomas by inducing the proliferation of lymphoma cells. 8,9 Mutations in exon 3 of A20 gene cause the risk of malignant T-cell acute lymphoblastic leukemia (T-ALL) 10 and chronic lymphocytic leukemia (CLL).…”

Section: Introductionmentioning

confidence: 99%

Prevalence of CYLD mutations in Vietnamese patients with polycythemia vera

Trang¹,

Giang²,

Trang³

et al. 2022

Adv Clin Exp Med

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Background. Polycythemia vera (PV) is characterized by increased proliferation and accumulation of erythroid and mature myeloid cells and megakaryocyte in the bone marrow and peripheral blood. The JAK2V617F mutation is present in most PV patients. Deubiquitinase (DUB) genes, including TNFAIP3 (A20), CYLD and Cezanne, function as negative regulators of inflammatory reaction through nuclear factor kappa-light-chainenhancer of activated B cells (NF-κB) signaling.Objectives. To determine single nucleotide polymorphisms (SNPs) profiling and gene expression of the DUB genes as well as the immunophenotype of PV cells. Material and methods.Seventy-seven patients with PV and 55 healthy individuals with well-characterized clinical profiles were enrolled. Gene expression profile was determined using quantitative real-time polymerase chain reaction (qRT-PCR), the immunophenotype with flow cytometry, secretion of cytokines using enzyme-linked immunosorbent assay (ELISA), and gene polymorphisms using direct DNA sequencing.Results. Inactivation of A20, CYLD and Cezanne, and increases in interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) levels, as well as the enhanced number of CD25 + CD4 T, Th1 and regulatory T cells were observed in PV patients. The genetic analysis of the CYLD gene identified 11 SNPs, in which a novel W736G nsSNP in exon 15 and a SNP c.2483+6 T>G in intron 15 were observed in PV cases with the frequencies of 18.2% and 5.2%, respectively. The W736G non-synonymous SNP (nsSNP) was found to be most likely to exert deleterious effect and the intronic SNP c.2483+6 T>G was identified as aberrant splicing. Sequencing of Cezanne gene identified 7 SNPs in intron 10 and PV carriers of the SNPs had at least 2 SNPs in this gene. Importantly, PV carriers of the W736G nsSNP had multiple SNPs in CYLD, but not in A20 or Cezanne gene.Conclusions. Two identified SNPs, including the W736G nsSNP and the SNP c.2483+6 T>G, in CYLD gene might be associated with a risk of PV disease, in which the deleterious effect of the W736G nsSNP in CYLD gene could contribute to the pathogenesis of PV.

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Regulation of NF-κB- and STAT1-mediated plasmacytoid dendritic cell functions by A20

Cited by 9 publications

References 32 publications

Nobiletin promotes the pyroptosis of breast cancer via regulation of miR‐200b/JAZF1 axis

Nobiletin promotes the pyroptosis of breast cancer via regulation of miR‐200b/JAZF1 axis

The regulatory role of peripheral blood mononuclear cell function by A20

Prevalence of CYLD mutations in Vietnamese patients with polycythemia vera

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