The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, China.
Center for Xin'an Medicine and Modernization of Traditional Chinese Medicine of IHM, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, China.
Lupus. 2024 Oct;33(11):1176-1191. doi: 10.1177/09612033241273072. Epub 2024 Aug 9.
We aim to investigate the potential roles of key genes in the development of lupus nephritis (LN), screen key biomarkers, and construct the lncRNA XIST/miR-381-3P/STAT1 axis by using bioinformatic prediction combined with clinical validation, thereby providing new targets and insights for clinical research.
Gene expression microarrays GSE157293 and GSE112943 were downloaded from the GEO database to obtain differentially expressed genes (DEGs), followed by enrichment analyses on these DEGs, which were enriched and analyzed to construct a protein-protein interaction (PPI) network to screen core genes. The lncRNA-miRNA-mRNA regulatory network was predicted and constructed based on the miRNA database. 37 female patients with systemic lupus erythematosus (SLE) were recruited to validate the bioinformatics results by exploring the diagnostic value of the target ceRNA axis in LN by dual luciferase and real-time fluorescence quantitative PCR (RT-qPCR) and receiver operating characteristic (ROC).
The data represented that a total of 133 differential genes were screened in the GSE157293 dataset and 2869 differential genes in the GSE112943 dataset, yielding a total of 26 differentially co-expressed genes. Six core genes (STAT1, OAS2, OAS3, IFI44, DDX60, and IFI44L) were screened. Biological functional analysis identified key relevant pathways in LN. ROC curve analysis suggested that lncRNA XIST, miR-381-3P, and STAT1 could be used as potential molecular markers to assist in the diagnosis of LN.
STAT1 is a key gene in the development of LN. In conclusion, lncRNA XIST, miR-381-3P, and STAT1 can be used as new molecular markers to assist in the diagnosis of LN, and the lncRNA XIST/miR-381-3P/STAT1 axis may be a potential therapeutic target for LN.
通过生物信息学预测结合临床验证，研究关键基因在狼疮肾炎（LN）发病机制中的潜在作用，筛选关键生物标志物，构建 lncRNA XIST/miR-381-3P/STAT1 轴，为临床研究提供新的靶点和思路。
从 GEO 数据库中下载基因表达微阵列 GSE157293 和 GSE112943，获取差异表达基因（DEGs），对这些 DEGs 进行富集分析，构建蛋白质-蛋白质相互作用（PPI）网络筛选核心基因。基于 miRNA 数据库预测并构建 lncRNA-miRNA-mRNA 调控网络。招募 37 例女性系统性红斑狼疮（SLE）患者，通过双荧光素酶和实时荧光定量 PCR（RT-qPCR）及受试者工作特征（ROC）曲线分析，验证靶向 ceRNA 轴在 LN 中的诊断价值。
GSE157293 数据集共筛选出 133 个差异基因，GSE112943 数据集共筛选出 2869 个差异基因，共得到 26 个差异共表达基因。筛选出 6 个核心基因（STAT1、OAS2、OAS3、IFI44、DDX60 和 IFI44L）。生物功能分析确定了 LN 中关键的相关通路。ROC 曲线分析表明，lncRNA XIST、miR-381-3P 和 STAT1 可作为潜在的分子标志物辅助 LN 的诊断。
STAT1 是 LN 发病机制中的关键基因。总之，lncRNA XIST、miR-381-3P 和 STAT1 可以作为新的分子标志物辅助 LN 的诊断，lncRNA XIST/miR-381-3P/STAT1 轴可能是 LN 的潜在治疗靶点。
