Aberrant expression of long non‑coding RNAs in peripheral blood mononuclear cells isolated from patients with gouty arthritis

Zhong,Xiaowu; Zhong,Xiaowu; Zhong,Xiaowu; Peng,Yuanhong; Peng,Yuanhong; Peng,Yuanhong; Liao,Hebin; Liao,Hebin; Liao,Hebin; Yao,Chengjiao; Yao,Chengjiao; Yao,Chengjiao; Li,Jiulong; Li,Jiulong; Li,Jiulong; Yang,Qibin; Yang,Qibin; Yang,Qibin; He,Yonglong; He,Yonglong; He,Yonglong; Qing,Yufeng; Qing,Yufeng; Qing,Yufeng; Guo,Xiaolan; Guo,Xiaolan; Guo,Xiaolan; Zhou,Jingguo; Zhou,Jingguo; Zhou,Jingguo

doi:10.3892/etm.2019.7816

Aberrant expression of long non‑coding RNAs in peripheral blood mononuclear cells isolated from patients with gouty arthritis

Authors:
- Xiaowu Zhong
- Yuanhong Peng
- Hebin Liao
- Chengjiao Yao
- Jiulong Li
- Qibin Yang
- Yonglong He
- Yufeng Qing
- Xiaolan Guo
- Jingguo Zhou
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Affiliations: Department of Clinical Laboratory, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China, Department of Rheumatology and Immunology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China, Translational Medicine Research Center, North Sichuan Medical College, Nanchong, Sichuan 637007, P.R. China, Department of Rheumatology and Immunology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan 610000, P.R. China
Published online on: July 26, 2019 https://doi.org/10.3892/etm.2019.7816
Pages: 1967-1976
Copyright: © Zhong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Gouty arthritis (GA) is the most common inflammatory and immune‑associated disease, and its prevalence and incidence exhibit yearly increases. The aim of the present study was to analyse the expression profile variation of long non‑coding RNAs (lncRNAs) in GA patients and to explore the role of lncRNAs in the pathogenesis of GA. The peripheral blood mononuclear cells of GA patients and of healthy controls (HCs) were used to detect for the differentially expressed lncRNAs by microarray. The functional annotations and classifications of the differentially expressed transcripts were predicted using Gene Ontology (GO) and pathway analysis. The results were then verified by reverse transcription‑quantitative (RT‑q)PCR. A total of 1,815 lncRNAs and 971 mRNAs with a >2‑fold difference in the levels of expression in the GA patients compared with those in the HCs were identified. According to the GO functional enrichment analysis, the differentially expressed lncRNAs were accumulated in terms including protein binding, catalytic activity and molecular transducer activity. The pathways predicted to be involved were the tumor necrosis factor signaling pathway, osteoclast differentiation, NOD‑like receptor signaling pathway and NF‑κB signaling pathway. The expression of six lncRNAs was measured by RT‑qPCR and the results were consistent with those of the microarrays. Among these lncRNAs, AJ227913 was the most differentially expressed lncRNA in GA patients vs. HCs. The expression of several lncRNAs was significantly changed in GA patients compared with that in HCs, which suggests that these lncRNAs with differential expression levels may have an important role in the development and progression of GA.

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1	Richette P and Bardin T: Gout. Lancet. 375:318–328. 2010. View Article : Google Scholar : PubMed/NCBI
2	Kuo CF, Grainge MJ, Zhang W and Doherty M: Global epidemiology of gout: Prevalence, incidence and risk factors. Nat Rev Rheumatol. 11:649–662. 2015. View Article : Google Scholar : PubMed/NCBI
3	Zhang X, Yang X, Wang M, Li X, Xia Q, Xu S, Xu J, Cai G, Wang L, Xin L, et al: Association between SLC2A9 (GLUT9) gene polymorphisms and gout susceptibility: An updated meta-analysis. Rheumatol Int. 36:1157–1165. 2016. View Article : Google Scholar : PubMed/NCBI
4	Matsuo H, Takada T, Ichida K, Nakamura T, Nakayama A, Ikebuchi Y, Ito K, Kusanagi Y, Chiba T, Tadokoro S, et al: Common defects of ABCG2, a high-capacity urate exporter, cause gout: A function-based genetic analysis in a Japanese population. Sci Transl Med. 1:5ra112009. View Article : Google Scholar : PubMed/NCBI
5	Tan PK, Farrar JE, Gaucher EA and Miner JN: Coevolution of URAT1 and uricase during primate evolution: Implications for serum urate homeostasis and gout. Mol Biol Evol. 33:2193–2200. 2016. View Article : Google Scholar : PubMed/NCBI
6	Pennisi E: Cell biology. Lengthy RNAs earn respect as cellular players. Science. 344:10722014. View Article : Google Scholar : PubMed/NCBI
7	Wang C, Wang L, Ding Y, Lu X, Zhang G, Yang J, Zheng H, Wang H, Jiang Y and Xu L: LncRNA structural characteristics in epigenetic regulation. Int J Mol Sci. 18:E26592017. View Article : Google Scholar : PubMed/NCBI
8	Saha P, Verma S, Pathak RU and Mishra RK: Long Noncoding RNAs in mammalian development and diseases. Adv Exp Med Biol. 1008:155–198. 2017. View Article : Google Scholar : PubMed/NCBI
9	Kwok ZH and Tay Y: Long noncoding RNAs: lincs between human health and disease. Biochem Soc Trans. 45:805–812. 2017. View Article : Google Scholar : PubMed/NCBI
10	Khanna D, Khanna PP, Fitzgerald JD, Singh MK, Bae S, Neogi T, Pillinger MH, Merill J, Lee S, Prakash S, et al: 2012 American college of rheumatology guidelines for management of gout. Part 2: Therapy and anti-inflammatory prophylaxis of acute gouty arthritis. Arthritis Care Res (Hoboken). 64:1447–1461. 2012. View Article : Google Scholar : PubMed/NCBI
11	Gomez JA, Wapinski OL, Yang YW, Bureau JF, Gopinath S, Monack DM, Chang HY, Brahic M and Kirkegaard K: The NeST Long ncRNA controls microbial susceptibility and epigenetic activation of the interferon-gamma locus. Cell. 152:743–754. 2013. View Article : Google Scholar : PubMed/NCBI
12	Lai F, Orom UA, Cesaroni M, Beringer M, Taatjes DJ, Blobel GA and Shiekhattar R: Activating RNAs associate with Mediator to enhance chromatin architecture and transcription. Nature. 494:497–501. 2013. View Article : Google Scholar : PubMed/NCBI
13	Poliseno L, Salmena L, Zhang J, Carver B, Haveman WJ and Pandolfi PP: A coding-independent function of gene and pseudogene mRNAs regulates tumour biology. Nature. 465:1033–1038. 2010. View Article : Google Scholar : PubMed/NCBI
14	The Gene Ontology Consortium: Expansion of the Gene Ontology knowledgebase and resources. Nucleic Acids Res. 45(D1): D331–D338. 2017. View Article : Google Scholar : PubMed/NCBI
15	Kanehisa M, Furumichi M, Tanabe M, Sato Y and Morishima K: KEGG: New perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 45:D353–D361. 2017. View Article : Google Scholar : PubMed/NCBI
16	Schmittgen TD and Livak KJ: Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 3:1101–1108. 2008. View Article : Google Scholar : PubMed/NCBI
17	Kalliolias GD and Ivashkiv LB: TNF biology, pathogenic mechanisms and emerging therapeutic strategies. Nat Rev Rheumatol. 12:49–62. 2016. View Article : Google Scholar : PubMed/NCBI
18	Shapiro F: Bone development and its relation to fracture repair. The role of mesenchymal osteoblasts and surface osteoblasts. Eur Cell Mater. 15:53–76. 2008. View Article : Google Scholar : PubMed/NCBI
19	Qing YF, Zhang QB and Zhou JG: Innate immunity functional gene polymorphisms and gout susceptibility. Gene. 524:412–414. 2013. View Article : Google Scholar : PubMed/NCBI
20	Mattick JS: Non-coding RNAs: The architects of eukaryotic complexity. EMBO Rep. 2:986–991. 2001. View Article : Google Scholar : PubMed/NCBI
21	Stachurska A, Zorro MM, van der Sijde MR and Withoff S: Small and long regulatory RNAs in the immune system and immune diseases. Front Immunol. 5:5132014. View Article : Google Scholar : PubMed/NCBI
22	Luo Q, Li X, Xu C, Zeng L, Ye J, Guo Y, Huang Z and Li J: Integrative analysis of long non-coding RNAs and messenger RNA expression profiles in systemic lupus erythematosus. Mol Med Rep. 17:3489–3496. 2018.PubMed/NCBI
23	Li LJ, Zhao W, Tao SS, Li J, Xu SZ, Wang JB, Leng RX, Fan YG, Pan HF and Ye DQ: Comprehensive long non-coding RNA expression profiling reveals their potential roles in systemic lupus erythematosus. Cell Immunol. 319:17–27. 2017. View Article : Google Scholar : PubMed/NCBI
24	Wang P, Xue Y, Han Y, Lin L, Wu C, Xu S, Jiang Z, Xu J, Liu Q and Cao X: The STAT3-binding long noncoding RNA lnc-DC controls human dendritic cell differentiation. Science. 344:310–313. 2014. View Article : Google Scholar : PubMed/NCBI
25	Wu GC, Li J, Leng RX, Li XP, Li XM, Wang DG, Pan HF and Ye DQ: Identification of long non-coding RNAs GAS5, linc0597 and lnc-DC in plasma as novel biomarkers for systemic lupus erythematosus. Oncotarget. 8:23650–23663. 2017.PubMed/NCBI
26	Pan F, Zhu L, Lv H and Pei C: Quercetin promotes the apoptosis of fibroblast-like synoviocytes in rheumatoid arthritis by upregulating lncRNA MALAT1. Int J Mol Med. 38:1507–1514. 2016. View Article : Google Scholar : PubMed/NCBI
27	Spurlock CF III, Tossberg JT, Matlock BK, Olsen NJ and Aune TM: Methotrexate inhibits NF-κB activity via long intergenic (noncoding) RNA-p21 induction. Arthritis Rheumatol. 66:2947–2957. 2014. View Article : Google Scholar : PubMed/NCBI
28	Liu Q, Zhang X, Dai L, Hu X, Zhu J, Li L, Zhou C and Ao Y: Long noncoding RNA related to cartilage injury promotes chondrocyte extracellular matrix degradation in osteoarthritis. Arthritis Rheumatol. 66:969–978. 2014. View Article : Google Scholar : PubMed/NCBI
29	Wang CL, Peng JP and Chen XD: LncRNA-CIR promotes articular cartilage degeneration in osteoarthritis by regulating autophagy. Biochem Biophys Res Commun. 505:692–698. 2018. View Article : Google Scholar : PubMed/NCBI
30	Mount DB: The kidney in hyperuricemia and gout. Curr Opin Nephrol Hypertens. 22:216–223. 2013. View Article : Google Scholar : PubMed/NCBI
31	Prasad Sah OS and Qing YX: Associations between hyperuricemia and chronic kidney disease: A Review. Nephrourol Mon. 7:e272332015. View Article : Google Scholar : PubMed/NCBI
32	Georganas C, Liu H, Perlman H, Hoffmann A, Thimmapaya B and Pope RM: Regulation of IL-6 and IL-8 expression in rheumatoid arthritis synovial fibroblasts: The dominant role for NF-kappa B but not C/EBP beta or c-Jun. J Immunol. 165:7199–7206. 2000. View Article : Google Scholar : PubMed/NCBI
33	De Benedetti F, Pignatti P, Bernasconi S, Gerloni V, Matsushima K, Caporali R, Montecucco CM, Sozzani S, Fantini F and Martini A: Interleukin 8 and monocyte chemoattractant protein-1 in patients with juvenile rheumatoid arthritis. Relation to onset types, disease activity, and synovial fluid leukocytes. J Rheumatol. 26:425–431. 1999.PubMed/NCBI
34	Lun SW, Wong CK, Tam LS, Li EK and Lam CW: Decreased ex vivo produxtion of TNF-alpha and IL-8 by peripheral blood cells of patients with rheumatoid arthritis after infliximab therapy. Int Immuno pharmacol. 7:1668–1677. 2007. View Article : Google Scholar
35	König A, Krenn V, Gillitzer R, Glöckner J, Janssen E, Gohlke F, Eulert J and Müller-Hermelink HK: Inflammatory infiltrate and interleukin-8 expression in the synovium of psoriatic arthritis-an immunohistochemical and mRNA analysis. Rheumatol Int. 17:159–168. 1997. View Article : Google Scholar : PubMed/NCBI
36	Biasi D, Carletto A, Caramaschi P, Bellavite P, Maleknia T, Scambi C, Favalli N and Bambara LM: Neutrophil functions and IL-8 in psoriatic arthritis and in cutaneous psoriasis. Inflammation. 22:533–543. 1998. View Article : Google Scholar : PubMed/NCBI
37	Tsai YC and Tsai TF: Anti-interleukin and interleukin therapies for psoriasis: Current evidence and clinical usefulness. Ther Adv Musculoskelet Dis. 9:277–294. 2017. View Article : Google Scholar : PubMed/NCBI
38	Kienhorst LB, van Lochem E, Kievit W, Dalbeth N, Merriman ME, Phipps-Green A, Loof A, van Heerde W, Vermeulen S, Stamp LK, et al: Gout is a chronic inflammatory disease in which high levels of interleukin-8 (CXCL8), myeloid-related protein 8/myeloid-related protein 14 complex, and an altered proteome are associated with diabetes mellitus and cardiovascular disease. Arthritis Rheumatol. 67:3303–3313. 2015. View Article : Google Scholar : PubMed/NCBI
39	Hachicha M, Naccache PH and McColl SR: Inflammatory microcrystals differentially regulate the secretion of macrophage inflammatory protein 1 and interleukin 8 by human neutrophils: A possible mechanism of neutrophil recruitment to sites of inflammation in synovitis. J Exp Med. 182:2019–2025. 1995. View Article : Google Scholar : PubMed/NCBI
40	Nishimura A, Akahoshi T, Takahashi M, Takagishi K, Itoman M, Kondo H, Takahashi Y, Yokoi K, Mukaida N and Matsushima K: Attenuation of monosodium urate crystal-induced arthritis in rabbits by a neutralizing antibody against interleukin-8. J Leukoc Biol. 62:444–449. 1997. View Article : Google Scholar : PubMed/NCBI