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类风湿关节炎的分子谱分析:一项整合基因表达研究中hsa_circ_0092125的表达动态

Molecular profiling of rheumatoid Arthritis: Expression dynamics of hsa_circ_0092125 and in an integrative gene expression study.

作者信息

Golestanifar Ahmad, Khedri Hengameh, Saberiyan Mohammadreza, Masroor Arezo

机构信息

Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.

Department of Medical Genetics, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.

出版信息

Biochem Biophys Rep. 2025 Jul 28;43:102180. doi: 10.1016/j.bbrep.2025.102180. eCollection 2025 Sep.

Abstract

BACKGROUND

Rheumatoid arthritis (RA) is a systemic autoimmune disorder marked by chronic synovial inflammation and progressive joint damage. Increasing evidence points to non-coding RNAs, particularly circular RNAs (circRNAs), as crucial regulators of immune and inflammatory responses in RA. However, their functional roles and clinical relevance remain incompletely understood.

METHODS

We conducted an integrative analysis combining bioinformatics and experimental validation to investigate the expression profiles of circRNAs and their host genes in RA. Transcriptomic datasets (GSE124373, GSE169082, GSE189338) were analyzed to identify differentially expressed mRNAs, circRNAs, and miRNAs in PBMCs of RA patients. Functional enrichment, protein-protein interaction (PPI) network construction, and competing endogenous RNA (ceRNA) regulatory analyses were performed. Subsequently, qPCR validation was carried out in clinical samples from 25 RA patients and 25 healthy controls.

RESULTS

Analysis revealed 1366 differentially expressed mRNAs, 47 circRNAs, and 223 miRNAs. Notably, and its host gene were significantly upregulated in RA samples. The ceRNA network indicated their involvement in immune-inflammatory pathways. qPCR validation confirmed elevated expression of (fold change = 4.35,  = 0.0114) and (fold change = 2.23,  = 0.0048). ROC (Receiver Operating Characteristic) curve analysis demonstrated moderate diagnostic value, particularly for (area under the curve (AUC) = 0.7824).

CONCLUSION

Our integrative bioinformatics and experimental approach identify and as potential biomarkers for RA. These findings enhance our understanding of the molecular mechanisms underlying RA pathogenesis and suggest new avenues for biomarker development and targeted therapies.

摘要

背景

类风湿性关节炎(RA)是一种全身性自身免疫性疾病,其特征为慢性滑膜炎症和进行性关节损伤。越来越多的证据表明,非编码RNA,尤其是环状RNA(circRNA),是RA免疫和炎症反应的关键调节因子。然而,它们的功能作用和临床相关性仍未完全明确。

方法

我们进行了一项整合生物信息学和实验验证的分析,以研究RA中circRNA及其宿主基因的表达谱。分析转录组数据集(GSE124373、GSE169082、GSE189338),以鉴定RA患者外周血单核细胞(PBMC)中差异表达的mRNA、circRNA和miRNA。进行功能富集、蛋白质-蛋白质相互作用(PPI)网络构建和竞争性内源RNA(ceRNA)调控分析。随后,对25例RA患者和25例健康对照的临床样本进行qPCR验证。

结果

分析发现1366个差异表达的mRNA、47个circRNA和223个miRNA。值得注意的是, 及其宿主基因在RA样本中显著上调。ceRNA网络表明它们参与免疫炎症途径。qPCR验证证实 (倍数变化 = 4.35, = 0.0114)和 (倍数变化 = 2.23, = 0.0048)表达升高。ROC(受试者工作特征)曲线分析显示具有中等诊断价值,尤其是对于 (曲线下面积(AUC) = 0.7824)。

结论

我们的整合生物信息学和实验方法确定 和 为RA的潜在生物标志物。这些发现加深了我们对RA发病机制分子机制的理解,并为生物标志物开发和靶向治疗提出了新途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32f5/12328782/83893667ba78/gr1.jpg

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