The high expression of miR-564 in patients with systemic lupus erythematosus promotes differentiation and maturation of DC cells by negatively regulating TP53 expression in vitro
Restricted accessResearch articleFirst published online August, 2021
The high expression of miR-564 in patients with systemic lupus erythematosus promotes differentiation and maturation of DC cells by negatively regulating TP53 expression in vitro
miRNA is involved in the occurrence and progression of systemic lupus erythematosus (SLE), but the regulatory effect of miRNA on dendritic cells in SLE patients is still unclear.
Material and methods
Bioinformatics methods were used to analyze the differentially expressed miRNA and its target genes in SLE patients. In vitro experiments were conducted to explore the effects and mechanisms of differentially expressed miRNAs in SLE patients on the differentiation and maturation of monocyte-derived dendritic cells.
Results
Bioinformatics analysis showed that miR-564 was up-regulated in SLE patients, and TP53 was the core target gene of miR-564. The expression level of miR-564 showed a rising trend during the differentiation and maturation of monocytes into Mo-DC cells. The differentiation, maturation and proliferation of Mo-DC cells were significantly inhibited by transfection with miR-564 antagomir. The expression of TP53 is negatively regulated by miR-564. In rescue experiments, the proliferation and migration of DC cells were significantly restored by co-transfection of miR-564 antagomir and TP53 si-RNA.
Conclusion
Highly expressed miR-564 promotes the maturation, proliferation of Mo-DC cells by negatively regulating the expression of TP53.
ThongBOlsenNJ.Systemic lupus erythematosus diagnosis and management. Rheumatology (Oxford)2017;
56: i3–i13.
2.
ShiXYeLXuS, et al.
Downregulated miR‑29a promotes B cell overactivation by upregulating Crk‑like protein in systemic lupus erythematosus. Mol Med Rep2020;
22: 841–849.
3.
HuangZPangGHuangYGLiC.miR-133 inhibits proliferation and promotes apoptosis by targeting LASP1 in lupus nephritis. Exp Mol Pathol2020;
114: 104384.
4.
WangMChenHQiuJ, et al.
Antagonizing miR-7 suppresses B cell hyperresponsiveness and inhibits lupus development. J Autoimmun2020;
109: 102440.
5.
HouacineSKangAParkinsonEKWanHFortuneF.Induction of p53 in keratinocyte cultures treated with Behçet's patient sera. J Oral Pathol Med2020;
49: 435–442.
6.
LevineAJ.P53 and the immune response: 40 years of exploration-a plan for the future. Int J Mol Sci2020;
21: 541.
7.
YangJZhuJMWuS, et al.
Association study between the TP53 Rs1042522G/C polymorphism and susceptibility to systemic lupus erythematosus in a Chinese Han population. Rheumatol Int2017;
37: 523–529.
8.
ChengTDingSLiuSLiYSunL.Human umbilical cord-derived mesenchymal stem cell therapy ameliorates lupus through increasing CD4+ T cell senescence via MiR-199a-5p/Sirt1/p53 axis. Theranostics2021;
11: 893–905.
9.
RitprajakPKaewraemruaenCHirankarnN.Current paradigms of tolerogenic dendritic cells and clinical implications for systemic lupus erythematosus. Cells2019;
8: 1291.
10.
KlarquistJZhouZShenNJanssenEM.Dendritic cells in systemic lupus erythematosus: from pathogenic players to therapeutic tools. Mediators Inflamm2016;
2016: 5045248.
11.
XuSJHuHTLiHLChangS.The role of miRNAs in immune cell development, immune cell activation, and tumor immunity: with a focus on macrophages and natural killer cells. Cells2019;
8: 1140.
12.
ZhouHWuL.The development and function of dendritic cell populations and their regulation by miRNAs. Protein Cell2017;
8: 501–513.
13.
TsuchiyaSYamabeMYamaguchiYKobayashiYKonnoTTadaK.Establishment and characterization of a human acute monocytic leukemia cell line (THP-1). Int J Cancer1980;
26: 171–176.
14.
ChanputWPetersVWichersH, et al. THP-1 and U937 cells. In: VerhoeckxKCotterPLópez-ExpósitoI (eds) The impact of food bioactives on health: in vitro and ex vivo models.
Cham:
Springer, 2015, pp.147–159.
15.
BoyetteLBMacedoCHadiK, et al.
Phenotype, function, and differentiation potential of human monocyte subsets. PLoS One2017;
12: e0176460.
16.
HuXZafarMIGaoF.Effects of histamine and its antagonists on murine T-cells and bone marrow-derived dendritic cells. Drug Des Dev Ther2015;
9: 4847–4860.
17.
N'DiayeMWarneckeAFlytzaniS, et al.
Rat bone marrow-derived dendritic cells generated with GM-CSF/IL-4 or FLT3L exhibit distinct phenotypical and functional characteristics. J Leukoc Biol2016;
99: 437–446.
18.
PejoskiDBallesterMAudersetF, et al.
Site-Specific DC surface signatures influence CD4(+) T cell Co-stimulation and Lung-Homing. Front Immunol2019;
10: 1650.
19.
InagakiSTakahashiMFukunagaYTakahashiH.HTLV-I-infected breast milk macrophages inhibit monocyte differentiation to dendritic cells. Viral Immunol2012;
25: 106–116.
20.
QianZDHuangLLZhuXM.An immunohistochemical study of CD83- and CD1a-positive dendritic cells in the decidua of women with recurrent spontaneous abortion. Eur J Med Res2015;
20: 2.
21.
SoutoGRMatiasMDPNunesLFMFerreiraRCMesquitaRA.Mature dendritic cell density is affected by smoking habit, lesion size, and epithelial dysplasia in oral leukoplakia samples. Arch Oral Biol2018;
95: 51–57.
22.
JinFHuHXuM, et al.
Serum microRNA profiles serve as novel biomarkers for autoimmune diseases. Front Immunol2018;
9: 2381.
23.
QuZLiWFuB.MicroRNAs in autoimmune diseases. Biomed Res Int2014;
2014: 527895.
24.
ShumnalievaRKachakovaDShoumnalieva-IvanovaVMitevaPKanevaRMonovS.Whole peripheral blood miR-146a and miR-155 expression levels in systemic lupus erythematosus patients. Acta Reumatol Port2018;
43: 217–225.
25.
ZengLWuJLLiuLM, et al.
Serum miRNA-371b-5p and miRNA-5100 act as biomarkers for systemic lupus erythematosus. Clin Immunol2018;
196: 103–109.
26.
CaoWQianGLuoW, et al.
miR-125b is downregulated in systemic lupus erythematosus patients and inhibits autophagy by targeting UVRAG. Biomed Pharmacother2018;
99: 791–797.
27.
MaycockG.Accident modelling and economic evaluation. Accid Anal Prev1986;
18: 169–174.
28.
ZhouCZhaoLWangK, et al.
MicroRNA-146a inhibits NF-κB activation and pro-inflammatory cytokine production by regulating IRAK1 expression in THP-1 cells. Exp Ther Med2019;
18: 3078–3084.
BorchersATLeibushorNNaguwaSMCheemaGSShoenfeldYGershwinME.Lupus nephritis: a critical review. Autoimmun Rev2012;
12: 174–194.
37.
MellmanI.Dendritic cells: master regulators of the immune response. Cancer Immunol Res2013;
1: 145–149.
38.
Muñoz-FontelaCMandinovaAAaronsonSALeeSW.Emerging roles of p53 and other tumour-suppressor genes in immune regulation. Nat Rev Immunol2016;
16: 741–750.
39.
JinYHofsethABCuiX, et al.
American ginseng suppresses colitis through p53-mediated apoptosis of inflammatory cells. Cancer Prev Res (Phila)2010;
3: 339–347.
40.
ChoiSEParkYSKohHC.NF-κB/p53-activated inflammatory response involves in diquat-induced mitochondrial dysfunction and apoptosis. Environ Toxicol2018;
33: 1005–1018.
41.
AkPLevineAJ.p53 and NF-κB: different strategies for responding to stress lead to a functional antagonism. FASEB J2010;
24: 3643–3652.
42.
LoweJMMenendezDBushelPR, et al.
p53 and NF-κB coregulate proinflammatory gene responses in human macrophages. Cancer Res2014;
74: 2182–2192.
43.
MatsumotoATakeishiSNakayamaKI.p57 regulates T-cell development and prevents lymphomagenesis by balancing p53 activity and pre-TCR signaling. Blood2014;
123: 3429–3439.
44.
HerkelJMimranAErezN, et al.
Autoimmunity to the p53 protein is a feature of systemic lupus erythematosus (SLE) related to anti-DNA antibodies. J Autoimmun2001;
17: 63–69.
45.
ZhongWXuXZhuZ, et al.
Increased interleukin-17A levels promote rituximab resistance by suppressing p53 expression and predict an unfavorable prognosis in patients with diffuse large B cell lymphoma. Int J Oncol2018;
52: 1528–1538.
