Sayed Noha H, Shaker Olfat G, Abd-Elmawla Mai A, Gamal Ahmed, Fathy Nevine
Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt.
Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University, Cairo, 11562, Egypt.
Clin Rheumatol. 2025 Feb;44(2):775-787. doi: 10.1007/s10067-024-07291-x. Epub 2025 Jan 11.
The current study was deployed to evaluate the role of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and miR-155, along with the inflammatory markers, TNFα and IL-6, and the adhesion molecule, cluster of differentiation 106 (CD106), in Behçet's disease (BD) pathogenesis. The study also assessed MALAT1/miR-155 as promising diagnostic and prognostic biomarkers for BD. The current retrospective case-control study included 74 Egyptian BD patients and 50 age and sex-matched controls. Blood samples were collected, and then, serum samples were separated for further biochemical and molecular investigations. The gene expression of MALAT1 and miR-155 was measured using qRT-PCR, whereas the levels of TNFα, IL-6, and CD106 were estimated using ELISA technique. MALAT1 was significantly downregulated, whereas miR-155 was upregulated among BD patients, compared with control subjects. Levels of TNFα, IL-6, and CD106 were elevated in BD patients. Further downregulation in MALAT1 together with upregulation of miR-155 was observed in active BD patients, relative to the inactive group. Receiver-operating-characteristic analysis revealed that MALAT1 and miR-155 could discriminate BD patients from controls, on the one hand, and active from inactive BD patients, on the other hand. MALAT1 was negatively correlated with TNFα, IL-6, and CD106, while miR-155 was positively correlated with them. Logistic regression analyses demonstrated miR-155 as a significant independent predictor of BD susceptibility, and MALAT1 as an independent negative predictor of BD activity. For the first time, the current research enlightens the role of MALAT1 and miR-155 in BD pathogenesis via impacting IL-6/TNF-α/CD-106 signaling. As well, MALAT1 and miR-155 could be regarded as novel non-invasive biomarkers that may improve BD diagnosis and prognosis. Key Points •MALAT1/miR-155 exerts potential role in Behçet's disease. •MALAT1/miR-155 are promising biomarkers for Behçet's disease. •MALAT1/miR-155 targets IL-6/TNF-α/CD-106 signaling.
本研究旨在评估转移相关肺腺癌转录本1(MALAT1)和miR-155,以及炎症标志物肿瘤坏死因子α(TNFα)和白细胞介素-6(IL-6),和黏附分子分化簇106(CD106)在白塞病(BD)发病机制中的作用。该研究还评估了MALAT1/miR-155作为BD有前景的诊断和预后生物标志物。当前这项回顾性病例对照研究纳入了74例埃及BD患者和50例年龄及性别匹配的对照。采集血样,然后分离血清样本用于进一步的生化和分子研究。使用qRT-PCR检测MALAT1和miR-155的基因表达,而使用ELISA技术测定TNFα、IL-6和CD106的水平。与对照受试者相比,BD患者中MALAT1显著下调,而miR-155上调。BD患者中TNFα、IL-6和CD106的水平升高。相对于非活动组,活动期BD患者中观察到MALAT1进一步下调以及miR-155上调。受试者工作特征分析显示,一方面,MALAT1和miR-155可以区分BD患者与对照,另一方面,可以区分活动期与非活动期BD患者。MALAT1与TNFα、IL-6和CD106呈负相关,而miR-155与它们呈正相关。逻辑回归分析表明,miR-155是BD易感性的显著独立预测因子,而MALAT1是BD活动度的独立负向预测因子。本研究首次揭示了MALAT1和miR-155通过影响IL-6/TNF-α/CD-106信号通路在BD发病机制中的作用。此外,MALAT1和miR-155可被视为新型非侵入性生物标志物,可能改善BD的诊断和预后。要点•MALAT1/miR-155在白塞病中发挥潜在作用。•MALAT1/miR-155是白塞病有前景的生物标志物。•MALAT1/miR-155靶向IL-6/TNF-α/CD-106信号通路。