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Published in: Arthritis Research & Therapy 1/2018

Open Access 01-12-2018 | Research article

Long noncoding RNA expression profile and association with SLEDAI score in monocyte-derived dendritic cells from patients with systematic lupus erythematosus

Authors: Yilun Wang, Shuang Chen, Sunyi Chen, Juan Du, Jinran Lin, Haihong Qin, Jie Wang, Jun Liang, Jinhua Xu

Published in: Arthritis Research & Therapy | Issue 1/2018

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Abstract

Background

Monocyte-derived dendritic cells (moDCs) play important roles in the pathogenesis of systemic lupus erythematosus (SLE). Aberrant expression of long noncoding RNAs (lncRNAs) could affect the function of moDCs. The aim of this study was to explore the lncRNA expression profile in moDCs of SLE patients to provide new insights into SLE.

Methods

LncRNA and mRNA microarrays were performed to identify differentially expressed lncRNAs and mRNAs in moDCs of SLE patients compared with normal controls. Bioinformatics analysis was also performed. Quantitative polymerase chain reaction (qPCR) was used to validate the results, and correlation analysis was used to analyze the relationship between these aberrantly expressed lncRNAs and SLE disease activity index (SLEDAI) scores.

Results

According to the gene expression profiles, 163 lncRNAs were differentially expressed between SLE and normal controls, including 118 that were upregulated and 45 that were downregulated. A total of 137 mRNAs were differentially expressed in moDCs of patients with SLE, including 83 that were upregulated and 54 that were downregulated. Furthermore, qPCR data showed that lncRNA ENST00000604411.1 (18.23-fold, P < 0.001) and ENST00000501122.2 (1.96-fold, P < 0.001) were upregulated and the other two lncRNAs, lnc-HSFY2–3:3 (0.42-fold, P < 0.001) and lnc-SERPINB9–1:2 (0.50-fold, P = 0.040), were downregulated in moDCs of SLE patients. The expression levels of ENST00000604411.1 (r = 0.593, P = 0.020) and ENST00000501122.2 (r = 0.539, P = 0.038) were positively correlated with the SLEDAI score, respectively.

Conclusions

The results indicate that the abnormal expression of lncRNAs in moDCs may be involved in the pathological processes of SLE. The expression level of ENST00000604411.1 and ENST00000501122.2 may have potential value for the assessment of disease activity in SLE.
Appendix
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Literature
1.
go back to reference Mackern-Oberti JP, Llanos C, Riedel CA, Bueno SM, Kalergis AM. Contribution of dendritic cells to the autoimmune pathology of systemic lupus erythematosus. Immunology. 2015;146(4):497–507.CrossRefPubMedPubMedCentral Mackern-Oberti JP, Llanos C, Riedel CA, Bueno SM, Kalergis AM. Contribution of dendritic cells to the autoimmune pathology of systemic lupus erythematosus. Immunology. 2015;146(4):497–507.CrossRefPubMedPubMedCentral
2.
go back to reference Mahajan A, Herrmann M, Munoz LE. Clearance deficiency and cell death pathways: a model for the pathogenesis of SLE. Front Immunol. 2016;7:1–12.CrossRef Mahajan A, Herrmann M, Munoz LE. Clearance deficiency and cell death pathways: a model for the pathogenesis of SLE. Front Immunol. 2016;7:1–12.CrossRef
3.
go back to reference Klarquist J, Zhou Z, Shen N, Janssen EM. Dendritic cells in systemic lupus erythematosus: from pathogenic players to therapeutic tools. Mediat Inflamm. 2016;2016:5045248.CrossRef Klarquist J, Zhou Z, Shen N, Janssen EM. Dendritic cells in systemic lupus erythematosus: from pathogenic players to therapeutic tools. Mediat Inflamm. 2016;2016:5045248.CrossRef
4.
go back to reference Son M, Kim SJ, Diamond B. SLE-associated risk factors affect DC function. Immunol Rev. 2016;269(1):100–17.CrossRefPubMed Son M, Kim SJ, Diamond B. SLE-associated risk factors affect DC function. Immunol Rev. 2016;269(1):100–17.CrossRefPubMed
5.
go back to reference Chan VS, Nie YJ, Shen N, Yan S, Mok MY, Lau CS. Distinct roles of myeloid and plasmacytoid dendritic cells in systemic lupus erythematosus. Autoimmun Rev. 2012;11(12):890–7.CrossRefPubMed Chan VS, Nie YJ, Shen N, Yan S, Mok MY, Lau CS. Distinct roles of myeloid and plasmacytoid dendritic cells in systemic lupus erythematosus. Autoimmun Rev. 2012;11(12):890–7.CrossRefPubMed
6.
go back to reference Ding D, Mehta H, McCune WJ, Kaplan MJ. Aberrant phenotype and function of myeloid dendritic cells in systemic lupus erythematosus. J Immunol. 2006;177(9):5878–89.CrossRefPubMed Ding D, Mehta H, McCune WJ, Kaplan MJ. Aberrant phenotype and function of myeloid dendritic cells in systemic lupus erythematosus. J Immunol. 2006;177(9):5878–89.CrossRefPubMed
7.
go back to reference Estrada-Capetillo L, Hernandez-Castro B, Monsivais-Urenda A, Alvarez-Quiroga C, Layseca-Espinosa E, Abud-Mendoza C, Baranda L, Urzainqui A, Sanchez-Madrid F, Gonzalez-Amaro R. Induction of Th17 lymphocytes and Treg cells by monocyte-derived dendritic cells in patients with rheumatoid arthritis and systemic lupus erythematosus. Clin Dev Immunol. 2013;2013:584303.CrossRefPubMedPubMedCentral Estrada-Capetillo L, Hernandez-Castro B, Monsivais-Urenda A, Alvarez-Quiroga C, Layseca-Espinosa E, Abud-Mendoza C, Baranda L, Urzainqui A, Sanchez-Madrid F, Gonzalez-Amaro R. Induction of Th17 lymphocytes and Treg cells by monocyte-derived dendritic cells in patients with rheumatoid arthritis and systemic lupus erythematosus. Clin Dev Immunol. 2013;2013:584303.CrossRefPubMedPubMedCentral
8.
go back to reference Wang Y, Liang J, Qin H, Ge Y, Du J, Lin J, Zhu X, Wang J, Xu J. Elevated expression of miR-142-3p is related to the pro-inflammatory function of monocyte-derived dendritic cells in SLE. Arthritis Res Ther. 2016;18(1):263.CrossRefPubMedPubMedCentral Wang Y, Liang J, Qin H, Ge Y, Du J, Lin J, Zhu X, Wang J, Xu J. Elevated expression of miR-142-3p is related to the pro-inflammatory function of monocyte-derived dendritic cells in SLE. Arthritis Res Ther. 2016;18(1):263.CrossRefPubMedPubMedCentral
9.
go back to reference Wu HJ, Zhao M, Yoshimura A, Chang C, Lu QJ. Critical link between epigenetics and transcription factors in the induction of autoimmunity: a comprehensive review. Clinical Reviews in Allergy & Immunology. 2016;50(3):333–44.CrossRef Wu HJ, Zhao M, Yoshimura A, Chang C, Lu QJ. Critical link between epigenetics and transcription factors in the induction of autoimmunity: a comprehensive review. Clinical Reviews in Allergy & Immunology. 2016;50(3):333–44.CrossRef
10.
go back to reference Atianand MK, Caffrey DR, Fitzgerald KA. Immunobiology of long noncoding RNAs. Annu Rev Immunol. 2017;35:177–98.CrossRefPubMed Atianand MK, Caffrey DR, Fitzgerald KA. Immunobiology of long noncoding RNAs. Annu Rev Immunol. 2017;35:177–98.CrossRefPubMed
11.
go back to reference Faghihi MA, Modarresi F, Khalil AM, Wood DE, Sahagan BG, Morgan TE, Finch CE, Laurent GS, Kenny PJ, Wahlestedt C. Expression of a noncoding RNA is elevated in Alzheimer's disease and drives rapid feed-forward regulation of beta-secretase. Nat Med. 2008;14(7):723–30.CrossRefPubMedPubMedCentral Faghihi MA, Modarresi F, Khalil AM, Wood DE, Sahagan BG, Morgan TE, Finch CE, Laurent GS, Kenny PJ, Wahlestedt C. Expression of a noncoding RNA is elevated in Alzheimer's disease and drives rapid feed-forward regulation of beta-secretase. Nat Med. 2008;14(7):723–30.CrossRefPubMedPubMedCentral
12.
go back to reference Wang P, Xue Y, Han Y, Lin L, Wu C, Xu S, Jiang Z, Xu J, Liu Q, Cao X. The STAT3-binding long noncoding RNA lnc-DC controls human dendritic cell differentiation. Science. 2014;344(6181):310–3.CrossRefPubMed Wang P, Xue Y, Han Y, Lin L, Wu C, Xu S, Jiang Z, Xu J, Liu Q, Cao X. The STAT3-binding long noncoding RNA lnc-DC controls human dendritic cell differentiation. Science. 2014;344(6181):310–3.CrossRefPubMed
13.
go back to reference Xin JX, Li J, Feng Y, Wang LY, Zhang Y, Yang RC. Downregulation of long noncoding RNA HOTAIRM1 promotes monocyte/dendritic cell differentiation through competitively binding to endogenous miR-3960. Oncotargets Ther. 2017;10:1–9.CrossRef Xin JX, Li J, Feng Y, Wang LY, Zhang Y, Yang RC. Downregulation of long noncoding RNA HOTAIRM1 promotes monocyte/dendritic cell differentiation through competitively binding to endogenous miR-3960. Oncotargets Ther. 2017;10:1–9.CrossRef
15.
go back to reference Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, Tsai MC, Hung T, Argani P, Rinn JL, et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 2010;464(7291):1071–U1148.CrossRefPubMedPubMedCentral Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, Tsai MC, Hung T, Argani P, Rinn JL, et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 2010;464(7291):1071–U1148.CrossRefPubMedPubMedCentral
16.
go back to reference Kino T, Hurt DE, Ichijo T, Nader N, Chrousos GP. Noncoding RNA Gas5 is a growth arrest- and starvation-associated repressor of the glucocorticoid receptor. Sci Signal. 2010;3(107):ra8. Kino T, Hurt DE, Ichijo T, Nader N, Chrousos GP. Noncoding RNA Gas5 is a growth arrest- and starvation-associated repressor of the glucocorticoid receptor. Sci Signal. 2010;3(107):ra8.
17.
go back to reference Suarez-Gestal M, Calaza M, Endreffy E, Pullmann R, Ordi-Ros J, Sebastiani GD, Ruzickova S, Santos MJ, Papasteriades C, Marchini M, et al. Replication of recently identified systemic lupus erythematosus genetic associations: a case-control study. Arthritis Res Ther. 2009;11(3):R69. Suarez-Gestal M, Calaza M, Endreffy E, Pullmann R, Ordi-Ros J, Sebastiani GD, Ruzickova S, Santos MJ, Papasteriades C, Marchini M, et al. Replication of recently identified systemic lupus erythematosus genetic associations: a case-control study. Arthritis Res Ther. 2009;11(3):R69.
18.
go back to reference Zhang FF, Wu LL, Qian J, Qu B, Xia SW, La T, Wu YF, Ma JY, Zeng J, Guo Q, et al. Identification of the long noncoding RNA NEAT1 as a novel inflammatory regulator acting through MAPK pathway in human lupus. J Autoimmun. 2016;75:96–104.CrossRefPubMed Zhang FF, Wu LL, Qian J, Qu B, Xia SW, La T, Wu YF, Ma JY, Zeng J, Guo Q, et al. Identification of the long noncoding RNA NEAT1 as a novel inflammatory regulator acting through MAPK pathway in human lupus. J Autoimmun. 2016;75:96–104.CrossRefPubMed
19.
go back to reference Yang HX, Liang NX, Wang M, Fei YY, Sun J, Li ZY, Xu Y, Guo C, Cao ZL, Li SQ, et al. Long noncoding RNA MALAT-1 is a novel inflammatory regulator in human systemic lupus erythematosus. Oncotarget. 2017;8(44):77400–6.PubMedPubMedCentral Yang HX, Liang NX, Wang M, Fei YY, Sun J, Li ZY, Xu Y, Guo C, Cao ZL, Li SQ, et al. Long noncoding RNA MALAT-1 is a novel inflammatory regulator in human systemic lupus erythematosus. Oncotarget. 2017;8(44):77400–6.PubMedPubMedCentral
20.
go back to reference Wu Y, Zhang F, Ma J, Zhang X, Wu L, Qu B, Xia S, Chen S, Tang Y, Shen N. Association of large intergenic noncoding RNA expression with disease activity and organ damage in systemic lupus erythematosus. Arthritis Res Ther. 2015;17:131.CrossRefPubMedPubMedCentral Wu Y, Zhang F, Ma J, Zhang X, Wu L, Qu B, Xia S, Chen S, Tang Y, Shen N. Association of large intergenic noncoding RNA expression with disease activity and organ damage in systemic lupus erythematosus. Arthritis Res Ther. 2015;17:131.CrossRefPubMedPubMedCentral
21.
go back to reference Wu GC, Li J, Leng RX, Li XP, Li XM, Wang DG, Pan HF, Ye DQ. Identification of long non-coding RNAs GAS5, linc0597 and lnc-DC in plasma as novel biomarkers for systemic lupus erythematosus. Oncotarget. 2017;8(14):23650–63.PubMedPubMedCentral Wu GC, Li J, Leng RX, Li XP, Li XM, Wang DG, Pan HF, Ye DQ. Identification of long non-coding RNAs GAS5, linc0597 and lnc-DC in plasma as novel biomarkers for systemic lupus erythematosus. Oncotarget. 2017;8(14):23650–63.PubMedPubMedCentral
22.
go back to reference Luo Q, Li X, Xu C, Zeng L, Ye J, Guo Y, Huang Z, Li J. Integrative analysis of long non-coding RNAs and messenger RNA expression profiles in systemic lupus erythematosus. Mol Med Rep. 2018;17(3):3489–96.PubMed Luo Q, Li X, Xu C, Zeng L, Ye J, Guo Y, Huang Z, Li J. Integrative analysis of long non-coding RNAs and messenger RNA expression profiles in systemic lupus erythematosus. Mol Med Rep. 2018;17(3):3489–96.PubMed
23.
go back to reference Li LJ, Zhao W, Tao SS, Li J, Xu SZ, Wang JB, Leng RX, Fan YG, Pan HF, Ye DQ. Comprehensive long non-coding RNA expression profiling reveals their potential roles in systemic lupus erythematosus. Cell Immunol. 2017;319:17–27.CrossRefPubMed Li LJ, Zhao W, Tao SS, Li J, Xu SZ, Wang JB, Leng RX, Fan YG, Pan HF, Ye DQ. Comprehensive long non-coding RNA expression profiling reveals their potential roles in systemic lupus erythematosus. Cell Immunol. 2017;319:17–27.CrossRefPubMed
24.
go back to reference Wang ZZ, Jinnin M, Nakamura K, Harada M, Kudo H, Nakayama W, Inoue K, Nakashima T, Honda N, Fukushima S, et al. Long non-coding RNA TSIX is upregulated in scleroderma dermal fibroblasts and controls collagen mRNA stabilization. Exp Dermatol. 2016;25(2):131–6.CrossRefPubMed Wang ZZ, Jinnin M, Nakamura K, Harada M, Kudo H, Nakayama W, Inoue K, Nakashima T, Honda N, Fukushima S, et al. Long non-coding RNA TSIX is upregulated in scleroderma dermal fibroblasts and controls collagen mRNA stabilization. Exp Dermatol. 2016;25(2):131–6.CrossRefPubMed
25.
go back to reference Gayen S, Maclary E, Buttigieg E, Hinten M, Kalantry S. A primary role for the Tsix lncRNA in maintaining random X-chromosome inactivation. Cell Rep. 2015;11(8):1251–65.CrossRefPubMedPubMedCentral Gayen S, Maclary E, Buttigieg E, Hinten M, Kalantry S. A primary role for the Tsix lncRNA in maintaining random X-chromosome inactivation. Cell Rep. 2015;11(8):1251–65.CrossRefPubMedPubMedCentral
26.
go back to reference McCombe PA, Greer JM, Mackay IR. Sexual dimorphism in autoimmune disease. Curr Mol Med. 2009;9(9):1058–79.CrossRefPubMed McCombe PA, Greer JM, Mackay IR. Sexual dimorphism in autoimmune disease. Curr Mol Med. 2009;9(9):1058–79.CrossRefPubMed
27.
go back to reference Zhang F, Wu L, Qian J, Qu B, Xia S, La T, Wu Y, Ma J, Zeng J, Guo Q et al. Identification of the long noncoding RNA NEAT1 as a novel inflammatory regulator acting through MAPK pathway in human lupus. J Autoimmun. 2016;75:96–104. Zhang F, Wu L, Qian J, Qu B, Xia S, La T, Wu Y, Ma J, Zeng J, Guo Q et al. Identification of the long noncoding RNA NEAT1 as a novel inflammatory regulator acting through MAPK pathway in human lupus. J Autoimmun. 2016;75:96–104.
28.
go back to reference Imamura K, Imamachi N, Akizuki G, Kumakura M, Kawaguchi A, Nagata K, Kato A, Kawaguchi Y, Sato H, Yoneda M, et al. Long noncoding RNA NEAT1-dependent SFPQ relocation from promoter region to Paraspeckle mediates IL8 expression upon immune stimuli. Mol Cell. 2014;53(3):393–406.CrossRefPubMed Imamura K, Imamachi N, Akizuki G, Kumakura M, Kawaguchi A, Nagata K, Kato A, Kawaguchi Y, Sato H, Yoneda M, et al. Long noncoding RNA NEAT1-dependent SFPQ relocation from promoter region to Paraspeckle mediates IL8 expression upon immune stimuli. Mol Cell. 2014;53(3):393–406.CrossRefPubMed
29.
go back to reference Guttman M, Amit I, Garber M, French C, Lin MF, Feldser D, Huarte M, Zuk O, Carey BW, Cassady JP, et al. Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature. 2009;458(7235):223–7.CrossRefPubMedPubMedCentral Guttman M, Amit I, Garber M, French C, Lin MF, Feldser D, Huarte M, Zuk O, Carey BW, Cassady JP, et al. Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature. 2009;458(7235):223–7.CrossRefPubMedPubMedCentral
30.
go back to reference Carpenter S, Aiello D, Atianand MK, Ricci EP, Gandhi P, Hall LL, Byron M, Monks B, Henry-Bezy M, Lawrence JB, et al. A long noncoding RNA mediates both activation and repression of immune response genes. Science. 2013;341(6147):789–92.CrossRefPubMedPubMedCentral Carpenter S, Aiello D, Atianand MK, Ricci EP, Gandhi P, Hall LL, Byron M, Monks B, Henry-Bezy M, Lawrence JB, et al. A long noncoding RNA mediates both activation and repression of immune response genes. Science. 2013;341(6147):789–92.CrossRefPubMedPubMedCentral
31.
go back to reference Carpenter S, Fitzgerald KA. Cytokines and long noncoding RNAs. Cold Spring Harb Perspect Biol. 2018;10(6). Carpenter S, Fitzgerald KA. Cytokines and long noncoding RNAs. Cold Spring Harb Perspect Biol. 2018;10(6).
32.
go back to reference Bengtsson AA, Ronnblom L. Role of interferons in SLE. Best Pract Res Clin Rheumatol. 2017;31(3):415–28.CrossRefPubMed Bengtsson AA, Ronnblom L. Role of interferons in SLE. Best Pract Res Clin Rheumatol. 2017;31(3):415–28.CrossRefPubMed
33.
go back to reference Niewold TB, Kelly JA, Flesch MH, Espinoza LR, Harley JB, Crow MK. Association of the IRF5 risk haplotype with high serum interferon-alpha activity in systemic lupus erythematosus patients. Arthritis Rheum. 2008;58(8):2481–7.CrossRefPubMedPubMedCentral Niewold TB, Kelly JA, Flesch MH, Espinoza LR, Harley JB, Crow MK. Association of the IRF5 risk haplotype with high serum interferon-alpha activity in systemic lupus erythematosus patients. Arthritis Rheum. 2008;58(8):2481–7.CrossRefPubMedPubMedCentral
34.
go back to reference Lee-Kirsch MA, Gong M, Chowdhury D, Senenko L, Engel K, Lee YA, de Silva U, Bailey SL, Witte T, Vyse TJ, et al. Mutations in the gene encoding the 3’-5’ DNA exonuclease TREX1 are associated with systemic lupus erythematosus. Nat Genet. 2007;39(9):1065–7.CrossRefPubMed Lee-Kirsch MA, Gong M, Chowdhury D, Senenko L, Engel K, Lee YA, de Silva U, Bailey SL, Witte T, Vyse TJ, et al. Mutations in the gene encoding the 3’-5’ DNA exonuclease TREX1 are associated with systemic lupus erythematosus. Nat Genet. 2007;39(9):1065–7.CrossRefPubMed
35.
go back to reference Chan VSF, Nie YJ, Shen N, Yan S, Mok MY, Lau CS. Distinct roles of myeloid and plasmacytoid dendritic cells in systemic lupus erythematosus. Autoimmun Rev. 2012;11(12):890–7.CrossRefPubMed Chan VSF, Nie YJ, Shen N, Yan S, Mok MY, Lau CS. Distinct roles of myeloid and plasmacytoid dendritic cells in systemic lupus erythematosus. Autoimmun Rev. 2012;11(12):890–7.CrossRefPubMed
Metadata
Title
Long noncoding RNA expression profile and association with SLEDAI score in monocyte-derived dendritic cells from patients with systematic lupus erythematosus
Authors
Yilun Wang
Shuang Chen
Sunyi Chen
Juan Du
Jinran Lin
Haihong Qin
Jie Wang
Jun Liang
Jinhua Xu
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 1/2018
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/s13075-018-1640-x

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