Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran.
Department of Biology, Faculty of Science, Urmia University, Urmia, 5756151818, Iran.
Mol Biol Rep. 2024 Oct 19;51(1):1075. doi: 10.1007/s11033-024-10019-4.
Long non-coding RNAs (lncRNAs) have emerged as crucial regulators in various biological processes, including immune regulation and autoimmune pathologies. However, their specific significance in modulating the cytokine network in systemic lupus erythematosus (SLE) remains largely unexplored. This study assessed the expression patterns of immune-related lncRNAs, HOTAIR, and AC007278.3, along with their related protein-coding genes, TNF-α and IL18RAP, in nephritic SLE patients. Additionally, the potential of selected genes as diagnostic biomarkers for SLE was evaluated.
Blood samples were obtained from SLE patients (n = 30) and age-sex-matched healthy controls (HCs) (n = 60). Subsequently, RNA was isolated from peripheral blood mononuclear cells (PBMCs), and cDNA was synthesized to analyze the expression levels of the target genes using real-time PCR. The correlation analysis between the relative expressions of different genes was examined in both the patient and HC groups. The diagnostic potential of the lncRNAs was determined by calculating the Area Under the Curve of the Receiver Operating Characteristics (AUC of ROC), Cut-off, sensitivity, and specificity. Our results indicated a significant upregulation of lncRNAs AC007278.3 (fold change [FC] = 14.13, p-value < 0.0001) and HOTAIR (FC = 14.1, p-value < 0.0001). Correspondingly, their associated target genes, TNF-α and IL18RAP, were also overexpressed in patients (FC = 2.66 and FC = 5.18, respectively, p-value < 0.001). Notably, a strong positive correlation was observed between IL18RAP and AC007278.3 in SLE patients. Moreover, the AUC of ROC analyses underscored the diagnostic efficacy of AC007278.3 alone and combined with HOTAIR, yielding values of 0.89 and 0.86, respectively.
These findings highlight the potential immunoregulatory roles of lncRNAs AC007278.3 and HOTAIR, emphasizing their significance as promising diagnostic biomarkers and potential therapeutic targets for SLE. Additionally, they provide valuable insights into the molecular mechanisms underpinning the disease's pathogenesis.
长链非编码 RNA（lncRNA）已成为各种生物过程（包括免疫调节和自身免疫病理学）中的关键调节因子。然而，它们在调节系统性红斑狼疮（SLE）中的细胞因子网络方面的具体意义在很大程度上仍未得到探索。本研究评估了免疫相关 lncRNA、HOTAIR 和 AC007278.3 及其相关蛋白编码基因 TNF-α 和 IL18RAP 在肾炎性 SLE 患者中的表达模式。此外，还评估了选定基因作为 SLE 诊断生物标志物的潜力。
从 SLE 患者（n=30）和年龄性别匹配的健康对照者（HC）（n=60）中采集血液样本。随后，从外周血单核细胞（PBMC）中分离 RNA，并使用实时 PCR 分析目标基因的表达水平。在患者和 HC 组中检查了不同基因相对表达之间的相关性分析。通过计算接收者操作特征（ROC）曲线下面积（AUC of ROC）、Cut-off、敏感性和特异性来确定 lncRNA 的诊断潜力。我们的结果表明，lncRNA AC007278.3（倍数变化[FC]=14.13，p 值<0.0001）和 HOTAIR（FC=14.1，p 值<0.0001）显著上调。相应地，它们的相关靶基因 TNF-α 和 IL18RAP 在患者中也过度表达（FC=2.66 和 FC=5.18，p 值<0.001）。值得注意的是，在 SLE 患者中观察到 IL18RAP 与 AC007278.3 之间存在强烈的正相关。此外，ROC 分析的 AUC 强调了 AC007278.3 单独和与 HOTAIR 联合的诊断功效，分别为 0.89 和 0.86。
这些发现强调了 lncRNA AC007278.3 和 HOTAIR 的潜在免疫调节作用，强调了它们作为有希望的 SLE 诊断生物标志物和潜在治疗靶点的重要性。此外，它们为疾病发病机制的分子机制提供了有价值的见解。
