lncRNA MEG3 is downregulated in ankylosing spondylitis and associated with disease activity, hospitalization time and disease duration

Liu,Wei; Huang,Lili; Zhang,Cuiying; Liu,Zuozhong

doi:10.3892/etm.2018.6921

lncRNA MEG3 is downregulated in ankylosing spondylitis and associated with disease activity, hospitalization time and disease duration

Authors:
- Wei Liu
- Lili Huang
- Cuiying Zhang
- Zuozhong Liu
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Affiliations: Department of Orthopedics, Yongchuan Hospital of Chongqing Medical University, Chongqing 402160, P.R. China, Department of Infections, Yongchuan Hospital of Chongqing Medical University, Chongqing 402160, P.R. China, Department of Gynaecology and Obstetrics, Yongchuan Hospital of Chongqing Medical University, Chongqing 402160, P.R. China
Published online on: November 2, 2018 https://doi.org/10.3892/etm.2018.6921
Pages: 291-297
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Long non‑coding (lnc)RNA maternally expressed gene 3 (MEG3) has been proved to participate in osteoporosis, which features inverse pathological changes to those associated with spondylosis. The present study aimed to investigate the involvement of lncRNA MEG3 in ankylosing spondylitis. Blood and open sacroiliac joint biopsies were obtained from ankylosing spondylitis patients and healthy controls, and the expression of MEG3 in those tissues was detected by reverse‑transcription‑quantitative polymerase chain reaction analysis. Disease activity was evaluated according to the Ankylosing Spondylitis Disease Activity Score established by the International Association of Ankylosing Spondylitis. The diagnostic value of MEG3 expression for ankylosing spondylitis was evaluated by receiver operating characteristic curve analysis. The correlation between MEG3 expression and disease activity was assessed using Pearson correlation analysis. Furthermore, according to the median expression level of MEG3, patients were divided into high‑level and low‑level groups. The hospitalization time and re‑hospitalization rate within 2 years after discharge were compared between these two groups and differences in clinicopathological parameters between the two groups were analyzed using the chi‑square test. The results indicated that MEG3 was downregulated in ankylosing spondylitis patients compared with that in healthy controls. Furthermore, MEG3 expression levels may be used to effectively distinguish ankylosing spondylitis patients from healthy controls. The serum levels of MEG3 were not associated with the patients' age, sex or alcohol/tobacco consumption, but closely correlated with disease activity and disease duration. In addition, patients with higher expression levels of MEG3 had a shorter hospitalization time and a lower re‑hospitalization rate within 2 years after discharge It was concluded that lncRNA MEG3 is downregulated in ankylosing spondylitis patients and is associated with disease activity, time of hospitalization and disease duration.

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1	Braun J and Sieper J: Ankylosing spondylitis. Lancet. 369:1379–1390. 2007. View Article : Google Scholar : PubMed/NCBI
2	Atouf O, Benbouazza K, Brick C, Saoud B, Benseffaj N, Amine B, Hajjaj-Hassouni N and Essakalli M: Distribution of HLA class I and II genes in ankylosing spondylitis patients from Morocco. Pathol Biol (Paris). 60:e80–e83. 2012. View Article : Google Scholar : PubMed/NCBI
3	Gilgil E, Kaçar C, Tuncer T and Bütün B: The association of syndesmophytes with vertebral bone mineral density in patients with ankylosing spondylitis. J Rheumatol. 32:292–294. 2005.PubMed/NCBI
4	Braun J, Brandt J, Listing J, Zink A, Alten R, Golder W, Gromnica-Ihle E, Kellner H, Krause A, Schneider M, et al: Treatment of active ankylosing spondylitis with infliximab: A randomised controlled multicentre trial. Lancet. 359:1187–1193. 2002. View Article : Google Scholar : PubMed/NCBI
5	Mercer TR, Dinger ME and Mattick JS: Long non-coding RNAs: Insights into functions. Nat Rev Genet. 10:155–159. 2009. View Article : Google Scholar : PubMed/NCBI
6	Gibb EA, Brown CJ and Lam WL: The functional role of long non-coding RNA in human carcinomas. Mol cancer. 10:382011. View Article : Google Scholar : PubMed/NCBI
7	Gutschner T and Diederichs S: The hallmarks of cancer: A long non-coding RNA point of view. RNA Biol. 9:703–719. 2012. View Article : Google Scholar : PubMed/NCBI
8	Zhou Y, Zhang X and Klibanski A: MEG3 noncoding RNA: A tumor suppressor. J Mol Endocrinol. 48:R45–R53. 2012. View Article : Google Scholar : PubMed/NCBI
9	Wang Q, Li Y and Zhang Y, Ma L, Lin L, Meng J, Jiang L, Wang L, Zhou P and Zhang Y: LncRNA MEG3 inhibited osteogenic differentiation of bone marrow mesenchymal stem cells from postmenopausal osteoporosis by targeting miR-133a-3p. Biomed Pharmacother. 89:1178–1186. 2017. View Article : Google Scholar : PubMed/NCBI
10	Klingberg E, Nurkkala M, Carlsten H and Forsblad-d'Elia H: Biomarkers of bone metabolism in ankylosing spondylitis in relation to osteoproliferation and osteoporosis. J Rheumatol. 41:1349–1356. 2014. View Article : Google Scholar : PubMed/NCBI
11	van der Linden S, Valkenburg HA and Cats A: Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum. 27:361–368. 1984.
12	Lukas C, Landewe R, Sieper J, Dougados M, Davis J, Braun J, van der Linden S and van der Heijde D; Assessment of SpondyloArthritis international Society, . Development of an ASAS-endorsed disease activity score (ASDAS) in patients with ankylosing spondylitis. Ann Rheum Dis. 68:18–24. 2009. View Article : Google Scholar : PubMed/NCBI
13	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
14	Zhang C, Wang C, Jia Z, Tong W, Liu D, He C, Huang X and Xu W: Differentially expressed mRNAs, lncRNAs, and miRNAs with associated co-expression and ceRNA networks in ankylosing spondylitis. Oncotarget. 8:113543–113557. 2017.PubMed/NCBI
15	Xie Z, Li J, Wang P, Li Y, Wu X, Wang S, Su H, Deng W, Liu Z, Cen S, et al: Differential expression profiles of long noncoding RNA and mRNA of osteogenically differentiated mesenchymal stem cells in ankylosing spondylitis. J Rheumatol. 43:1523–1531. 2016. View Article : Google Scholar : PubMed/NCBI
16	Li X, Chai W, Zhang G, Ni M, Chen J, Dong J, Zhou Y, Hao L, Bai Y and Wang Y: Down-Regulation of lncRNA-AK001085 and its influences on the diagnosis of ankylosing spondylitis. Med Sci Monit. 23:11–16. 2017. View Article : Google Scholar : PubMed/NCBI
17	Miyakoshi N, Itoi E, Murai H, Wakabayashi I, Ito H and Minato T: Inverse relation between osteoporosis and spondylosis in postmenopausal women as evaluated by bone mineral density and semiquantitative scoring of spinal degeneration. Spine (Phila Pa 1976). 28:492–495. 2003. View Article : Google Scholar : PubMed/NCBI
18	Zhou X, Yin C, Dang Y, Ye F and Zhang G: Identification of the long non-coding RNA H19 in plasma as a novel biomarker for diagnosis of gastric cancer. Sci Rep. 5:115162015. View Article : Google Scholar : PubMed/NCBI
19	Soares do Amaral N, Cruz E, Melo N, de Melo Maia B and Malagoli Rocha R: Noncoding RNA profiles in tobacco-and alcohol-associated diseases. Genes (Basel). 8(pii): E62016. View Article : Google Scholar : PubMed/NCBI
20	Grammatikakis I, Panda AC, Abdelmohsen K and Gorospe M: Long noncoding RNAs (lncRNAs) and the molecular hallmarks of aging. Aging (Albany NY). 6:992–1009. 2014. View Article : Google Scholar : PubMed/NCBI
21	Ren S, Wang F, Shen J, Sun Y, Xu W, Lu J, Wei M, Xu C, Wu C, Zhang Z, et al: Long non-coding RNA metastasis associated in lung adenocarcinoma transcript 1 derived miniRNA as a novel plasma-based biomarker for diagnosing prostate cancer. Euro J Cancer. 49:2949–2959. 2013. View Article : Google Scholar
22	Goldberger C, Dulak J, Duftner C, Weidinger F, Falkenbach A and Schirmer M: Vascular endothelial growth factor (VEGF) in ankylosing spondylitis-a pilot study. Wien Med Wochenschr. 152:223–225. 2002. View Article : Google Scholar : PubMed/NCBI
23	Sveaas SH, Berg IJ, Provan SA, Semb AG, Olsen IC, Ueland T, Aukrust P, Vøllestad N, Hagen KB, Kvien TK and Dagfinrud H: Circulating levels of inflammatory cytokines and cytokine receptors in patients with ankylosing spondylitis: A cross-sectional comparative study. Scand J Rheumatol. 44:118–124. 2015. View Article : Google Scholar : PubMed/NCBI
24	Qiu GZ, Tian W, Fu HT, Li CP and Liu B: Long noncoding RNA-MEG3 is involved in diabetes mellitus-related microvascular dysfunction. Biochem Biophys Res Commun. 471:135–141. 2016. View Article : Google Scholar : PubMed/NCBI
25	Su W, Xie W, Shang Q and Su B: The long noncoding RNA MEG3 is downregulated and inversely associated with VEGF levels in osteoarthritis. Biomed Res Int. 2015:3568932015. View Article : Google Scholar : PubMed/NCBI