Volume 10, Issue 4 (Vol.10 No.4 Jan 2022)
rbmb.net 2022, 10(4): 527-536 |
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Shimaa Saad El-Din * 
, Laila Ahmed Rashed , Mervat Eissa , Ahmed Bahgat Eldemery , Omnia Abdelkareem Mohammed , Marwa Abdelgwad
, Laila Ahmed Rashed , Mervat Eissa , Ahmed Bahgat Eldemery , Omnia Abdelkareem Mohammed , Marwa Abdelgwad
The Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, Cairo, Egypt.
Abstract: (3093 Views)
Background: Circular RNA-HIPK3 (CircHIPK3) has been shown to be aberrantly expressed in a variety of diseases, contributing to disease initiation and progression. The aim of the present study is to investigate the role of the circHIPK3 RNA/microRNA-124a interaction in the pathogenesis of rheumatoid arthritis (RA).
Methods: This study included 79 RA patients and 30 control individuals. The patients involved were classified according to the disease activity score (DAS28) into mild (24 patients), moderate (24 patients), and severe (31 patients). Serum samples were collected to estimate the relative gene expression of circHIPK3 RNA and its target gene microRNA-124a by quantitative real time-PCR. Moreover, ELISA was used to detect the serum levels of monocyte chemoattractant protein-1 (MCP-1). Routine laboratory estimation of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and rheumatoid factor (RF) was also done.
Results: In all grades of RA groups, there was a significantly substantial elevation of circHIPK3 RNA gene expression, with subsequent downregulation of miRNA-124a when compared to the control group. CircHIPK3 and microRNA-124a expression have been established to be inversely linked. Also, estimation
of serum levels of MCP-1, ESR, CRP, and RF exhibited a significant increase in all grades of RA as compared to the control group.
Conclusions: CircHIPK3 and microRNA-124a might be regarded as key players in the pathogenesis of RA. The cross-talk between them appears to be responsible for inducing joint inflammation by increasing MCP-1 production. Targeting circHIPK3 and microRNA-124a, and their downstream adaptor molecules, poses a new challenge for RA therapy.
Methods: This study included 79 RA patients and 30 control individuals. The patients involved were classified according to the disease activity score (DAS28) into mild (24 patients), moderate (24 patients), and severe (31 patients). Serum samples were collected to estimate the relative gene expression of circHIPK3 RNA and its target gene microRNA-124a by quantitative real time-PCR. Moreover, ELISA was used to detect the serum levels of monocyte chemoattractant protein-1 (MCP-1). Routine laboratory estimation of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and rheumatoid factor (RF) was also done.
Results: In all grades of RA groups, there was a significantly substantial elevation of circHIPK3 RNA gene expression, with subsequent downregulation of miRNA-124a when compared to the control group. CircHIPK3 and microRNA-124a expression have been established to be inversely linked. Also, estimation
of serum levels of MCP-1, ESR, CRP, and RF exhibited a significant increase in all grades of RA as compared to the control group.
Conclusions: CircHIPK3 and microRNA-124a might be regarded as key players in the pathogenesis of RA. The cross-talk between them appears to be responsible for inducing joint inflammation by increasing MCP-1 production. Targeting circHIPK3 and microRNA-124a, and their downstream adaptor molecules, poses a new challenge for RA therapy.
Type of Article: Original Article |
Subject:
Molecular Biology
Received: 2021/09/5 | Accepted: 2021/09/5 | Published: 2022/02/7
Received: 2021/09/5 | Accepted: 2021/09/5 | Published: 2022/02/7
References
1. He J, Wang Y, Feng M, Zhang X, Jin YB, Li X, et al. Dietary intake and risk of rheumatoid arthritis-a cross section multicenter study. Clin Rheumatol. 2016;35(12):2901-2908. [DOI:10.1007/s10067-016-3383-x] [PMID] [PMCID]
2. Castro-Villegas C, Pérez-Sánchez C, Escudero A, Filipescu I, Verdu M, Ruiz-Limón P, et al. Circulating miRNAs as potential biomarkers of therapy effectiveness in rheumatoid arthritis patients treated with anti-TNFα. Arthritis Res Ther. 2015;17(1):49. [DOI:10.1186/s13075-015-0555-z] [PMID] [PMCID]
3. Singh RP, Massachi I, Manickavel S, Singh S, Rao NP, Hasan S, et al. The role of miRNA in inflammation and autoimmunity. Autoimmun Rev. 2013;12(12):1160-5. [DOI:10.1016/j.autrev.2013.07.003] [PMID]
4. Ansari-Moghaddam B, Asghar Kiani A, 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]
5. McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med. 2011;365(23):2205-19. [DOI:10.1056/NEJMra1004965] [PMID]
6. Jie LG, Huang RY, Sun WF, Wei S, Chu YL, Huang QC, et al. Role of cysteine rich angiogenic inducer 61 in fibroblast like synovial cell proliferation and invasion in rheumatoid arthritis. Mol Med Rep. 2015;11(2):917-23. [DOI:10.3892/mmr.2014.2770] [PMID] [PMCID]
7. Huang QC, Huang RY. The cyclooxygenase-2/thromboxane A2 pathway: a bridge from rheumatoid arthritis to lung cancer?. Cancer Lett. 2014;354(1):28-32. [DOI:10.1016/j.canlet.2014.08.024] [PMID]
8. Huang RY, Huang QC, Burgering BM. Novel insight into the role of alpha-actinin-1 in rheumatoid arthritis. Discov Med. 2014;17:75-80.
9. Nakasa T, Nagata Y, Yamasaki K, Ochi M. A mini-review: microRNA in arthritis. Physiol Genomics. 2011;43(10):566-70. [DOI:10.1152/physiolgenomics.00142.2010] [PMID]
10. Tong X, Zeng H, Gu P, Wang K, Zhang H, Lin X. Monocyte chemoattractant protein 1 promotes the proliferation, migration and differentiation potential of fibroblast like synoviocytes via the PI3K/P38 cellular signaling pathway. Mol Med Rep. 2020;21(3):1623-1632. [DOI:10.3892/mmr.2020.10969] [PMID]
11. Ospelt C, Gay S, Klein K. Epigenetics in the pathogenesis of RA. Semin Immunopathol. 2017;39(4):409-419. [DOI:10.1007/s00281-017-0621-5] [PMID]
12. Chen JQ, Papp G, Szodoray P, Zeher M. The role of microRNAs in the pathogenesis of autoimmune diseases. Autoimmun Rev. 2016;15(12):1171-1180. [DOI:10.1016/j.autrev.2016.09.003] [PMID]
13. Evangelatos G, Fragoulis GE, Koulouri V, Lambrou GI. MicroRNAs in rheumatoid arthritis: From pathogenesis to clinical impact. Autoimmun Rev. 2019;18(11):102391. [DOI:10.1016/j.autrev.2019.102391] [PMID]
14. 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]
15. Turner JD, Filer A. The role of the synovial fibroblast in rheumatoid arthritis pathogenesis. Curr Opin Rheumatol. 2015;27(2):175-82. [DOI:10.1097/BOR.0000000000000148] [PMID]
16. de la Rica L, Urquiza JM, Gomez-Cabrero D, Islam AB, Lopez-Bigas N, Tegner J, et al. Identification of novel markers in rheumatoid arthritis through integrated analysis of DNA methylation and microRNA expression. J Autoimmun. 2013;41:6-16. [DOI:10.1016/j.jaut.2012.12.005] [PMID]
17. Kawano S, Nakamachi Y. miR-124a as a key regulator of proliferation and MCP-1 secretion in synoviocytes from patients with rheumatoid arthritis. Ann Rheum Dis. 2011;70(Suppl 1):i88-91. [DOI:10.1136/ard.2010.138669] [PMID]
18. Wang Y, Dai L, Wu H, Zhang ZR, Wang WY, Fu J, et al. Novel anti-inflammatory target of geniposide: Inhibiting Itgbeta1/Ras-Erk1/2 signal pathway via the miRNA-124a in rheumatoid arthritis synovial fibroblasts. Int Immunopharmacol. 2018;65:284-294. [DOI:10.1016/j.intimp.2018.09.049] [PMID]
19. Nakamachi Y, Kawano S, Takenokuchi M, Nishimura K, Sakai Y, Chin T, et al. MicroRNA-124a is a key regulator of proliferation and monocyte chemoattractant protein 1 secretion in fibroblast-like synoviocytes from patients with rheumatoid arthritis. Arthritis Rheum. 2009;60(5):1294-304. [DOI:10.1002/art.24475] [PMID]
20. Wang M, Yu F, Wu W, Zhang Y, Chang W, Ponnusamy M, et al. Circular RNAs: A novel type of non-coding RNA and their potential implications in antiviral immunity. Int J Biol Sci. 2017;13(12):1497-1506. [DOI:10.7150/ijbs.22531] [PMID] [PMCID]
21. van Rossum D, Verheijen BM, Pasterkamp RJ. Circular RNAs: Novel Regulators of Neuronal Development. Front Mol Neurosci. 2016;9:74. [DOI:10.3389/fnmol.2016.00074] [PMID] [PMCID]
22. Tay Y, Rinn J, Pandolfi PP. The multilayered complexity of ceRNA crosstalk and competition. Nature. 2014;505:344-352. [DOI:10.1038/nature12986] [PMID] [PMCID]
23. Cheng J, Zhuo H, Xu M, Wang L, Xu H, Peng J, et al. Regulatory network of circRNA-miRNA-mRNA contributes to the histological classification and disease progression in gastric cancer. J Transl Med. 2018;16(1):216. [DOI:10.1186/s12967-018-1582-8] [PMID] [PMCID]
24. Zheng Q, Bao C, Guo W, Li S, Chen J, Chen B, et al. Circular RNA profiling reveals an abundant circHIPK3 that regulates cell growth by sponging multiple miRNAs. Nature Communications. 2016;7:11215. [DOI:10.1038/ncomms11215] [PMID] [PMCID]
25. Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd, et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010;62(9):2569-81. [DOI:10.1002/art.27584] [PMID]
26. 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]
27. Chan YH. Biostatistics102: Quantitative Data - Parametric & Non-parametric Tests. Singapore Medical Journal. 2003;44(8):391-396.
28. Arif K, Elliott EK, Haupt LM, Griffiths LR. Regulatory Mechanisms of Epigenetic miRNA Relationships in Human Cancer and Potential as Therapeutic Targets. Cancers (Basel). 2020;12(10):2922. [DOI:10.3390/cancers12102922] [PMID] [PMCID]
29. Huang X, Cen X, Zhang B, Liao Y, Zhu G, Liu J. Prospect of circular RNA in osteogenesis: A novel orchestrator of signaling pathways. J Cell Physiol. 2019;234(12):21450-21459. [DOI:10.1002/jcp.28866] [PMID]
30. Li HZ, Lin Z, Xu XH, Lin N, Lu HD. The potential roles of circRNAs in osteoarthritis: a coming journey to find a treasure. Biosci Rep. 2018;38(5):BSR20180542. [DOI:10.1042/BSR20180542] [PMID] [PMCID]
31. Panda AC. Circular RNAs Act as miRNA Sponges. Adv Exp Med Biol. 2018;1087:67-79. [DOI:10.1007/978-981-13-1426-1_6] [PMID]
32. Chen G, Tang W, Wang S, Long C, He X, Yang D, et al. Promising diagnostic and therapeutic circRNAs for skeletal and chondral disorders. Int J Biol Sci. 2021;17(5): 1428-1439. [DOI:10.7150/ijbs.57887] [PMID] [PMCID]
33. Wu Q, Yuan ZH, Ma XB, Tang XH. Low expression of CircRNA HIPK3 promotes osteoarthritis chondrocyte apoptosis by serving as a sponge of miR-124 to regulate SOX8. Eur Rev Med Pharmacol Sci. 2020;24(15):7937-7945.
34. Abdel Fatah W, Atef L, Mohamed A, Refaat D, Mohsen M, Abd El-Raof M, et al. Study of Serum Monocyte Chemoattractant Protein-1AS A Marker in Rheumatoid Arthritis. The Egyptian Journal of Hospital Medicine. 2014;56(1):321-332.
https://doi.org/10.21608/ejhm.2014.15691 [DOI:10.12816/0005579]
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