ASSOCIATION OF MICRO-RNA EXPRESSION PROFILES WITH DISEASE SEVERITY IN RHEUMATOID ARTHRITIS PATIENTS

Authors

  • Amna Noor Rawalpindi Medical University, Rawalpindi, Pakistan. Author
  • M. Hamza Ijaz Mohiuddin Islamic Medical University, Mirpur AJK, Pakistan. Author
  • Muhammad Moaaz Anwar Research Associate, Islamabad, Pakistan. Author
  • Saleh Aziz Khyber Medical University, Peshawar, Pakistan. Author
  • Haseeb Muhammad Khan Islamabad Medical & Dental College, Islamabad, Pakistan. Author https://orcid.org/0009-0008-5044-516X
  • Muhammad Hassan Hayatabad Medical Complex, Peshawar, Pakistan. Author

DOI:

https://doi.org/10.71000/7e7t7g87

Keywords:

Biomarkers, C-reactive protein, Disease activity, MicroRNAs, , Rheumatoid arthritis, Synovial inflammation, , Tumor necrosis factor-alpha

Abstract

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation, progressive joint destruction, and significant morbidity. Recent evidence suggests that microRNAs (miRNAs), small non-coding RNA molecules involved in gene regulation, may serve as promising biomarkers for disease activity and progression in RA.

Objective: To evaluate the association between circulating microRNA expression profiles and clinical severity in patients with rheumatoid arthritis.

Methods: A cross-sectional study was conducted over eight months at tertiary care hospitals in Lahore, Pakistan, enrolling 90 adult RA patients diagnosed based on ACR/EULAR 2010 criteria. Clinical disease activity was assessed using the DAS28-ESR score. Plasma levels of miR-146a, miR-155, miR-21, and miR-223 were quantified using real-time PCR. Statistical analyses included Pearson correlation, one-way ANOVA, and post hoc Tukey’s tests to explore associations between miRNA expression and disease severity and inflammatory markers.

Results: Higher expression levels of miR-146a (r = 0.48), miR-155 (r = 0.53), miR-21 (r = 0.41), and miR-223 (r = 0.46) significantly correlated with DAS28-ESR scores (p < 0.001 for all except miR-21, p = 0.002). Expression levels increased progressively with disease activity category. Significant positive correlations were also observed between these miRNAs and ESR and CRP values, with miR-155 showing the strongest association.

Conclusion: The study establishes a significant association between circulating miRNAs and RA disease severity. These miRNAs, particularly miR-155 and miR-146a, hold potential as non-invasive biomarkers for disease monitoring and personalized treatment strategies in rheumatoid arthritis.

Author Biographies

  • Amna Noor, Rawalpindi Medical University, Rawalpindi, Pakistan.

     Senior Demonstrator / Coordinator PhD Microbiology & Molecular Biology, Pathology Department, Rawalpindi Medical University, Rawalpindi, Pakistan.

  • M. Hamza Ijaz, Mohiuddin Islamic Medical University, Mirpur AJK, Pakistan.

    4th Year MBBS Student, Mohiuddin Islamic Medical University, Mirpur AJK, Pakistan.

  • Muhammad Moaaz Anwar, Research Associate, Islamabad, Pakistan.

    Research Associate, Islamabad, Pakistan.

  • Saleh Aziz, Khyber Medical University, Peshawar, Pakistan.

    Department of Medical Laboratory Technology, Hafeez Institute of Medical Sciences, Khyber Medical University, Peshawar, Pakistan.

  • Haseeb Muhammad Khan, Islamabad Medical & Dental College, Islamabad, Pakistan.

    Assistant Professor, Islamabad Medical & Dental College, Islamabad, Pakistan.

  • Muhammad Hassan, Hayatabad Medical Complex, Peshawar, Pakistan.

    Trainee Medical Officer, Hayatabad Medical Complex, Peshawar, Pakistan.

References

Ebrahimian H, Akhtari M, Akhlaghi M, Farhadi E, Jamshidi A, Alishiri GH, et al. Altered expression of apoptosis-related genes in rheumatoid arthritis peripheral blood mononuclear cell and related miRNA regulation. Immun Inflamm Dis. 2023;11(7):e914.

Gamal M, El-Diwany O, Abd Elhamed SS, Elshafei A, Hammad R. Association of circulating Treg and plasma microRNA-21 with rheumatoid arthritis progression. Egypt J Immunol. 2025;32(1):63-76.

Niu M, Li Y, Xu H, Yuan J, Yan M, Yang G, et al. Circ_0001715 Mediated Progression and Inflammation in Fibroblast-Like Synoviocytes of Rheumatoid Arthritis by Targeting miR-326/TLR-4-NF-κB Pathway. J Biochem Mol Toxicol. 2025;39(5):e70283.

Zhi L, Liang J, Huang W, Ma J, Qing Z, Wang X. Circ_AFF2 facilitates proliferation and inflammatory response of fibroblast-like synoviocytes in rheumatoid arthritis via the miR-375/TAB2 axis. Exp Mol Pathol. 2021;119:104617.

Li X, Qu M, Zhang J, Chen K, Ma X. CircASH2L facilitates tumor-like biologic behaviours and inflammation of fibroblast-like synoviocytes via miR-129-5p/HIPK2 axis in rheumatoid arthritis. J Orthop Surg Res. 2021;16(1):302.

Ciechomska M, Roszkowski L, Burakowski T, Massalska M, Felis-Giemza A, Roura AJ. Circulating miRNA-19b as a biomarker of disease progression and treatment response to baricitinib in rheumatoid arthritis patients through miRNA profiling of monocytes. Front Immunol. 2023;14:980247.

Ciechomska M, Wojtas B, Bonek K, Roszkowski L, Gluszko P, Benes V, et al. Comprehensive microRNA and transcriptomic profiling of rheumatoid arthritis monocytes: role of microRNA-146b in pro-inflammatory progression. Rheumatology (Oxford). 2021;60(11):5424-35.

Gosetti di Sturmeck T, Malimpensa L, Ferrazzano G, Belvisi D, Leodori G, Lembo F, et al. Exploring miRNAs' Based Modeling Approach for Predicting PIRA in Multiple Sclerosis: A Comprehensive Analysis. Int J Mol Sci. 2024;25(12).

Zhong S, Ouyang Q, Zhu D, Huang Q, Zhao J, Fan M, et al. Hsa_circ_0088036 promotes the proliferation and migration of fibroblast-like synoviocytes by sponging miR-140-3p and upregulating SIRT 1 expression in rheumatoid arthritis. Mol Immunol. 2020;125:131-9.

Qing P, Liu Y. Inhibitory role of long non-coding RNA OIP5-AS1 in rheumatoid arthritis progression through the microRNA-448-paraoxonase 1-toll-like receptor 3-nuclear factor κB axis. Exp Physiol. 2020;105(10):1708-19.

Faihan WA, Darweesh MF. Investigate role of miRNA146a and IL-17 level in progressive rheumatoid arthritis disease. Egypt J Immunol. 2024;31(3):71-80.

Hassani M, Dehani M, Zare Rafie M, Esmaeilzadeh E, Davar S, Pakzad B, et al. Investigation of rs531564 Polymorphism in the Primary MicroRNA-124 Gene in Patients with Systemic Lupus Erythematosus and Rheumatoid Arthritis: Association with Disease Susceptibility and Clinical Characteristics. Iran J Allergy Asthma Immunol. 2021;20(3):303-13.

Lu X, Yan S, Li X, Xue Y, Zhang L. LNCRNA 1197 Promotes the Progression of Fibroblast-Like Synovial Cells by Targeting miR-206 in Rheumatoid Arthritis Patients: A Pilot Study. Ann Clin Lab Sci. 2024;54(5):588-96.

Wang Y, Hou L, Yuan X, Xu N, Zhao S, Yang L, et al. LncRNA NEAT1 Targets Fibroblast-Like Synoviocytes in Rheumatoid Arthritis via the miR-410-3p/YY1 Axis. Front Immunol. 2020;11:1975.

Fu X, Song G, Ni R, Liu H, Xu Z, Zhang D, et al. LncRNA-H19 silencing suppresses synoviocytes proliferation and attenuates collagen-induced arthritis progression by modulating miR-124a. Rheumatology (Oxford). 2021;60(1):430-40.

Zheng J, Zeng P, Zhang H, Zhou Y, Liao J, Zhu W, et al. Long noncoding RNA ZFAS1 silencing alleviates rheumatoid arthritis via blocking miR-296-5p-mediated down-regulation of MMP-15. Int Immunopharmacol. 2021;90:107061.

Xie Z, Shen P, Qu Y, Xu J, Zheng C, Gao Y, et al. MiR-20a inhibits the progression of human arthritis fibroblast-like synoviocytes and inflammatory factor expression by targeting ADAM10. Environ Toxicol. 2020;35(8):867-78.

Wang QS, Fan KJ, Teng H, Liu J, Yang YL, Chen D, et al. MiR-204/-211 double knockout exacerbates rheumatoid arthritis progression by promoting splenic inflammation. Int Immunopharmacol. 2024;140:112850.

Yang Z, Hou N, Cheng W, Lu X, Wang M, Bai S, et al. MiR-378 exaggerates angiogenesis and bone erosion in collagen-induced arthritis mice by regulating endoplasmic reticulum stress. Cell Death Dis. 2024;15(12):910.

Wilson C, Swaroop P, Kumar S, Chopra A, Sharawat SK. Molecular leveraging of HOX-embedded non-coding RNAs in the progression of acute myeloid leukemia. Hum Cell. 2024;38(1):24.

El Maghraby HM, El-Mosely AM, Alian SM, Orabi EE, Azab MM, Nabil F. Nasal Carriage of enterotoxigenic Staphylococcus aureus and microRNA 146a expression profile in rheumatoid arthritis patients. Egypt J Immunol. 2025;32(2):44-56.

Tang J, Gao H, Liu Y, Song J, Feng Y, Wang G, et al. Network construction of aberrantly expressed miRNAs and their target mRNAs in ventricular myocardium with ischemia-reperfusion arrhythmias. J Cardiothorac Surg. 2020;15(1):216.

Yang J, Li Z, Wang L, Yun X, Zeng Y, Ng JPL, et al. The role of non-coding RNAs (miRNA and lncRNA) in the clinical management of rheumatoid arthritis. Pharmacol Res. 2022;186:106549.

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Published

2025-07-19