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Volume 10, Issue 4 (Vol.10 No.4 Jan 2022)
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Medhat E, Ayeldeen G, Hosni Ahmed H, Shaker O, Gheita T, Salma Ashour S. HOTAIR and THRIL Long Non Coding RNAs and Their Target Genes in Rheumatoid Arthritis patients. rbmb.net 2022; 10 (4) :697-710
URL: http://rbmb.net/article-1-785-en.html
URL: http://rbmb.net/article-1-785-en.html
Engy Medhat * 
, Ghada Ayeldeen , Hanan Hosni Ahmed , Olfat Shaker , Tamer Gheita , Sara Salma Ashour
, Ghada Ayeldeen , Hanan Hosni Ahmed , Olfat Shaker , Tamer Gheita , Sara Salma Ashour
Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University.
Abstract: (3030 Views)
Background: Rheumatoid arthtritis (RA) is a chronic systemic inflammatory autoimmune disease characterized by irreversible joint damage and deformity. The aim of this study is to investigate THRIL and HOTAIR serum expression and their target genes in Egyptian RA patients and to evaluate their relationship to the clinico-pathological data.
Methods: The present study included fifty-two RA patients and fifty-six healthy controls. RA patients were classified according to DAS28 score. All subjects were subjected to full history taking and clinical examination. Quantitative real time PCR was done to estimate the expression levels of serum THRIL and
HOTAIR as well as their target genes tumor necrosis factor alpha (TNF-α) and metalloproteinase 2 (MMP- 2) were estimated by ELISA techniques.
Results: Results revealed that both THRIL and HOTAIR were statistically over expressed in RA patients compared to healthy group with p-value< 0.05. Results showed as well that the target genes for those longnon coding RNAs, TNF-α and MMP-2, were also significantly higher in RA patients compared to healthy controls.
Conclusions: Both THRIL and HOTAIR associated with their target genes, can be considered as diagnostic markers for RA.
Methods: The present study included fifty-two RA patients and fifty-six healthy controls. RA patients were classified according to DAS28 score. All subjects were subjected to full history taking and clinical examination. Quantitative real time PCR was done to estimate the expression levels of serum THRIL and
HOTAIR as well as their target genes tumor necrosis factor alpha (TNF-α) and metalloproteinase 2 (MMP- 2) were estimated by ELISA techniques.
Results: Results revealed that both THRIL and HOTAIR were statistically over expressed in RA patients compared to healthy group with p-value< 0.05. Results showed as well that the target genes for those longnon coding RNAs, TNF-α and MMP-2, were also significantly higher in RA patients compared to healthy controls.
Conclusions: Both THRIL and HOTAIR associated with their target genes, can be considered as diagnostic markers for RA.
Keywords: HOTAIR, Matrix metalloproteinase 2 and tumor necrosis factor alpha, Rheumatoid arthritis, THRIL.
Type of Article: Original Article |
Subject:
Molecular Biology
Received: 2021/09/6 | Accepted: 2021/10/24 | Published: 2022/02/7
Received: 2021/09/6 | Accepted: 2021/10/24 | Published: 2022/02/7
References
1. Fang Q, Zhou C, Nandakumar KS. Molecular and Cellular Pathways Contributing to Joint Damage in Rheumatoid Arthritis. Mediators Inflamm. 2020;2020:3830212. [DOI:10.1155/2020/3830212] [PMID] [PMCID]
2. Scott DL, Wolfe F, Huizinga TW. Rheumatoid arthritis. The Lancet. 2010;376(9746):1094-1108. [DOI:10.1016/S0140-6736(10)60826-4]
3. De Rycke L, Peene I, Hoffman IE, Kruithof E, :union: A, Meheus L. Rheumatoid factor and anticitrullinated protein antibodies in rheumatoid arthritis: diagnostic value, associations with radiological progression rate, and extra-articular manifestations. Ann Rheum Dis. 2004;63(12):1587-93. [DOI:10.1136/ard.2003.017574] [PMID] [PMCID]
4. Pearson MJ, JonesSW. Review: long noncoding RNAs in the regulation of inflammatory pathways in rheumatoid arthritis and osteoarthritis. Arthritis Rheumatol. 2016;68(11):2575-2583. [DOI:10.1002/art.39759] [PMID] [PMCID]
5. Li Y, Li J, Chen L, Xu L. The roles of long non-coding RNA in osteoporosis. Curr Stem Cell Res Ther. 2020;15(7):639-645. [DOI:10.2174/1574888X15666200501235735] [PMID]
6. Kochi Y: Genetics of autoimmune diseases: perspectives from genome-wide association studies. Int Immunol. 2016;28(4):155-61. [DOI:10.1093/intimm/dxw002] [PMID] [PMCID]
7. Gupta R, Shah N, Wang K, Kim j, Hurling's H, Wong D, et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 2010;464(7291):1071-6. [DOI:10.1038/nature08975] [PMID] [PMCID]
8. Li Z, Chao TC, Chang KY, Lin N, Patil VS, Shimizu C, et al. The long noncoding RNA THRIL regulates TNFα expression through its interaction with hnRNPL. Proc Natl Acad Sci U S A. 2014;111(3):1002-7. [DOI:10.1073/pnas.1313768111] [PMID] [PMCID]
9. Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham 3rd CO, et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010;69(9):2569-81. [DOI:10.1002/art.27584] [PMID]
10. Prevoo ML, van't Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL. Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum. 1995;38(1):44-8. [DOI:10.1002/art.1780380107] [PMID]
11. Ansari-Moghaddam B, Kiani AA, Sheikhian A, Birjandi M, Ahmadi SAY, Mousavi N, et al. Rheumatoid Arthritis Susceptibility Is Associated with the KIR2DS4-Full of Killer-Cell Immunoglobulin-Like Receptor Genes in the Lur Population of Iran. Rep Biochem Mol Biol. 2021;10(1):84-94. [DOI:10.52547/rbmb.10.1.84] [PMID] [PMCID]
12. Wang J, Yan S, Yang J, Lu H, Xu D, Wang Z. Non-coding RNAs in Rheumatoid Arthritis: From Bench to Bedside. Front Immunol. 2020; 10:3129. [DOI:10.3389/fimmu.2019.03129] [PMID] [PMCID]
13. Song J, Kim D, Han J, Kim Y, Lee M, Jin E. PBMC and exosome-derived HOTAIR is a critical regulator and potent marker for rheumatoid arthritis. Clin Exp Med. 2015;15(1):121-6. [DOI:10.1007/s10238-013-0271-4] [PMID]
14. McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med. 2011;365(23):2205-19. [DOI:10.1056/NEJMra1004965] [PMID]
15. Schett G, Gravallese E. Bone erosion in rheumatoid arthritis: mechanisms, diagnosis and treatment. Nat Rev Rheumatol. 2012;8(11):656-64. [DOI:10.1038/nrrheum.2012.153] [PMID] [PMCID]
16. Moelants EA, Mortier A, Van Damme J, Proost P. Regulation of TNF-alpha with a focus on rheumatoid arthritis. Immunol Cell Biol. 2013;91(6):393-401. [DOI:10.1038/icb.2013.15] [PMID]
17. Brzustewicz E, Bryl E. The role of cytokines in the pathogenesis of rheumatoid arthritis, Practical and potential application of cytokines as biomarkers and targets of personalized therapy. Cytokine. 2015;76(2):527-536. [DOI:10.1016/j.cyto.2015.08.260] [PMID]
18. Nozawa K, Fujishiro M, Takasaki Y, Sekigawa I. Inhibition of rheumatoid arthritis by blocking connective tissue growth factor. World J Orthop. 2014;5(5):653-659. [DOI:10.5312/wjo.v5.i5.653] [PMID] [PMCID]
19. Milman N, Karsh J, Booth RA. Correlation of a multi- cytokine panel with clinical disease activity in patients with rheumatoid arthritis. Clin Biochem. 2010;43(16-17):1309-14. [DOI:10.1016/j.clinbiochem.2010.07.012] [PMID]
20. Wei ST, Sun YH, Zong SH, Xiang YB Serum. Levels of IL-6 and TNF-a May Correlate with Activity and Severity of Rheumatoid Arthritis. Med Sci Monit. 2015;21:4030-4038. [DOI:10.12659/MSM.895116] [PMID] [PMCID]
21. Hadinedoushan H, Noorbakhsh P, Soleymani-Salehabad H. Tumor Necrosis Factor Alpha Gene Polymorphism and Association With Its Serum Level in Iranian Population With Rheumatoid Arthritis. Arch Rheumatol. 2016;31(4):306-313. [DOI:10.5606/ArchRheumatol.2016.5907] [PMID] [PMCID]
22. Ebrahimi AA, Noshad H, Sadreddini S, Hejazi MS, Mohammadzadeh Sadigh Y, Eshraghi Y, et al. Serum Levels of TNF-α, TNF-αRI, TNF-αRII and IL-12 in Treated Rheumatoid Arthritis Patients. Iran J Immunol. 2009;6(3):147-53.
23. Bartok B, Firestein GS. Fibroblast-like synoviocytes: Key effector cells in rheumatoid arthritis. Immunol Rev. 2010;233(1):233-55. [DOI:10.1111/j.0105-2896.2009.00859.x] [PMID] [PMCID]
24. Filer A. The fibroblast as a therapeutic target in rheumatoid arthritis. Curr Opin Pharmacol. 2013;13:413-9. [DOI:10.1016/j.coph.2013.02.006] [PMID]
25. Frisenda S, Perricone C, Valesini G. Cartilage as a target of autoimmunity: A thin layer. Autoimmun Rev. 2013;12(5):591-8. [DOI:10.1016/j.autrev.2012.10.003] [PMID]
26. Charni-Ben TN, Desmarais S, Bay-Jensen AC, Delaissé JM, Percival M D, Garnero PThe. type II collagen fragments Helix-II and CTX-II reveal different enzymatic pathways of human cartilage collagen degradation. Osteoarthritis Cartilage. 2008;16(10):1183-91. [DOI:10.1016/j.joca.2008.02.008] [PMID]
27. Giannelli G, Erriquez R, Iannone F, Marinosci F, Lapadula G, Antonaci S. MMP-2, MMP-9, TIMP-1 and TIMP-2 levels in patients with rheumatoid arthritis and psoriatic arthritis. Clin Exp Rheumatol. 2004;22(3):335-8.
28. Chang YH, Lin IL, Tsay GJ, Yang SC, Yang TP, Ho KT, et al. Elevated circulatory MMP-2 and MMP-9 levels and activities in patients with rheumatoid arthritis and systemic lupus erythematosus. Clin Biochem. 2008;41(12):955-959. [DOI:10.1016/j.clinbiochem.2008.04.012] [PMID]
29. Angelotti F, Parma A, Cafaro G, Capecchi R, Alunno A, Puxeddu I. One year in review 2017: pathogenesis of rheumatoid arthritis. Clin Exp Rheumatol. 2017 May-Jun;35(3):368-378.
30. Kolarz B, Majdan M. Epigenetic aspects of rheumatoid arthritis: contribution of non-coding RNAs. Seminars in Arthritis and Rheumatism. 2017;46(6):724-731. [DOI:10.1016/j.semarthrit.2017.01.003] [PMID]
31. Shaker O, Mahfouz H, Salama A, Medhat E. Long Non-Coding HULC and miRNA-372 as Diagnostic Biomarkers in Hepatocellular Carcinoma. Rep Biochem Mol Biol. 2020;9(2):230-240. [DOI:10.29252/rbmb.9.2.230] [PMID] [PMCID]
32. Ponting CP, Oliver PL, Reik W. Evolution and functions of long noncoding RNAs. Cell. 2009;136(4):629-41. [DOI:10.1016/j.cell.2009.02.006] [PMID]
33. Klec C, Gutschner T, Panzitt K,Pickler M. Involvement of long noncoding RNA HULC (highly up-regulated in liver cancer) in pathogenesis and implications for therapeutic intervention. Expert Opin Ther Targets. 2019;23(3):177-186. [DOI:10.1080/14728222.2019.1570499] [PMID]
34. Xu F, Jin L, Jin Y, Nie Z, Zheng H. Long noncoding RNAs in autoimmune diseases. J Biomed Mater Res A. 2019;107(2):468-475. [DOI:10.1002/jbm.a.36562] [PMID]
35. Moharamoghli M, Hassan-Zadeh V, Dolatshahi E, Alizadeh Z, Farazmand A. The expression of GAS5, THRIL, and RMRP lncRNAs is increased in T cells of patients with rheumatoid arthritis. Clin Rheumatol. 2019;38(11):3073-3080 [DOI:10.1007/s10067-019-04694-z] [PMID]
36. Fouad NA, Shaker OG, Mohamed EA, El-Sayed HS, Hussein HA, Ahmed NA, et al. Diagnostic potential of metastasis-associated-lung-adenocarcinomatranscript-1 (MALAT-1) and TNFa and hnRNPL related immunoregulatory long non-coding RNA (THRIL) in systemic lupus erythematosus patients: Relation to disease activity. The Egyptian Rheumatologist. 2019;41:197-201. [DOI:10.1016/j.ejr.2018.11.002]
37. Shaker O, Mahmoud R, Abdelaleem O, Ahmed T, Fouad N, Hussein H, et al. Expression Profile of Long Noncoding RNAs, lnc-Cox2, and HOTAIR in Rheumatoid Arthritis Patients. J Interferon Cytokine Res. 2019;39(3):174-180. [DOI:10.1089/jir.2018.0117] [PMID]
38. Chu SC, Yang SF, Lue KH, Hsieh YS, Wu CL, Lu KH. Regulation of gelatinases expression by cytokines, endotoxin, and pharmacological agents in the human osteoarthritic knee. Connect Tissue Res. 2004;45(3):142-50. [DOI:10.1080/03008200490506058] [PMID]
39. Scian R, Barrionuevo P, Giambartolomei GH, De Simone EA, Vanzulli SI, Fossati CA, et al. Potential Role of Fibroblast-Like Synoviocytes in Joint Damage Induced by Brucella abortus Infection through Production and Induction of Matrix Metalloproteinases. Infect Immun. 2011;79(9):3619-32. [DOI:10.1128/IAI.05408-11] [PMID] [PMCID]
40. Wang Y, Yang L, Zhang J, Xue R, Tang Z, Huang W, et al. Differential MMP-2 activity induced by mechanical compression and inflammatory factors in human synoviocytes. Mol Cell Biomech. 2010;7(2):105-14.
41. Klimiuk PA, Sierakowski S, Latosiewicz R, Cylwik JP, Cylwik B, Skowronski J, et al. Circulating tumour necrosis factor alpha and soluble tumour necrosis factor receptors in patients with different patterns of rheumatoid synovitis. Ann Rheum Dis. 2003;62(5):472-475. [DOI:10.1136/ard.62.5.472] [PMID] [PMCID]
42. Manicourt DH, Triki R, Fukuda K, Devogelaer JP, Nagant de Deuxchaisnes C, Thonar EJ. Levels of circulating tumor necrosis factor a and interleukin-6 in patients with rheumatoid arthritis. Relationship to serum levels of hyaluronan and antigenic keratan sulfate. Arthritis Rheum. 1993;36(4):490-9. [DOI:10.1002/art.1780360409] [PMID]
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