MicroRNA-155 acts as a potential prognostic and diagnostic factor in patients with ankylosing spondylitis by modulating SOCS3

Background Ankylosing spondylitis (AS) is a progressive inflammatory disease. Our primary objective was to explore the role of miR-155 and its targeted factors in AS pathogenesis. Methods and results PBMCs were isolated from 30 AS patients and 30 healthy individuals using the Ficoll-hypaque isolatio...

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Veröffentlicht in:Molecular biology reports 2023, Vol.50 (1), p.553-563
Hauptverfasser: Jahangir, Mohammadsaleh, Kahrizi, Mohammad Saeed, Natami, Mohammad, Moaref Pour, Raziyeh, Ghoreishizadeh, Shadi, Hemmatzadeh, Maryam, Mohammadi, Hamed, Shomali, Navid, Sandoghchian Shotorbani, Siamak
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Sprache:eng
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Zusammenfassung:Background Ankylosing spondylitis (AS) is a progressive inflammatory disease. Our primary objective was to explore the role of miR-155 and its targeted factors in AS pathogenesis. Methods and results PBMCs were isolated from 30 AS patients and 30 healthy individuals using the Ficoll-hypaque isolation approach. The expression of miR-155 and its associated targets, including Suppressor Of Cytokine Signaling 3 (SOCS3), STAT3, and IL-21, were determined using qT-qPCR. Then, PBMCs were cultured, and the effect of miR-155, SOCS3 siRNA (to suppress its expression), pEFSOCS3 (enforced expression), and their combination were investigated by qRT-PCR and western blotting. We also treated the cultured PBMCs with Brefeldin A, a potent inhibitor of cytokine secretion, to determine its effect on IL-21 expression and secretion. In addition, the association between miR-155 and patients’ clinicopathological features was examined. The results showed that miR-155, IL-21, and STAT3 were increased in patients with AS, while SOCS3 had decreasing expression trend. It was also determined that miR-155 alleviates SOCS3 expression and increases IL-21 and STAT3 expression; it had a prominent effect when combined with SOCS3 siRNA. Besides, we showed that simultaneous transfection of miR-155 and pEFSOCS3 had no significant effect on IL-21 and STAT3 expression, revealing that miR-155 could alleviate the enforced expression of SOCS3. It was also proven that Brefledine A led to IL-21 up-regulation or accumulation while relieving its secretion. Also, a significant correlation between miR-155 and pathological features of AS patients was found. Conclusion miR-155 acts as a potential prognostic and diagnostic biomarker. Its up-regulation leads to the down-regulation of SOCS3 and increased expression of IL-21 and STAT3 as characteristic of TH-17 lymphocytes, leading to worsening inflammatory conditions in patients with AS.
ISSN:0301-4851
1573-4978
DOI:10.1007/s11033-022-08033-5