影响因子：4.6
文章题目：Mediating oxidative stress through the Palbociclib/miR-141-3p/STAT4 axis in osteoporosis: a bioinformatics and experimental validation study
DOI：10.1038/s41598-023-46813-6
第一作者：Jiajia Ji, Shaobo Wu, Xueyuan Bao, Shixuan Liu, Yuxing Ye, Jiayuan Liu, Jinniu Guo, Jiateng Liu, Xi Wang, Zhihao Xia, Liangliang Wei, Yan Zhang, Dingjun Hao, Dageng Huang
作者单位：
西安交通大学弘辉医院脊柱外科；
西安交通大学附属医院；
香港赛马会兽医学院传染病及公共卫生学系；
香港城市大学生命科学学院，中国香港第一转化医学中心
引用产品：
U96-1497E    Human IL-2 ELISA Kit      
U96-1523E    Human IL-12 ELISA Kit    
U96-1097E    Human IL-23 ELISA Kit    
U96-1899E    Human IL-27 ELISA Kit    
U96-1101E    Human IL-35 ELISA Kit  
文章摘要：
Osteoporosis is a common bone disease characterized by loss of bone mass, reduced bone strength, and deterioration of bone microstructure. ROS-induced oxidative stress plays an important role in osteoporosis. However, the biomarkers and molecular mechanisms of oxidative stress are still unclear. We obtained the datasets from the Gene Expression Omnibus (GEO) database, and performed differential analysis, Venn analysis, and weighted correlation network analysis (WGCNA) analysis out the hub genes. Then, the correlation between inflammatory factors and hub genes was analyzed, and a Mendelian randomization (MR) analysis was performed on cytokines and osteoporosis outcomes. In addition, “CIBERSORT” was used to analyze the infiltration of immune cells and single-cell RNA-seq data was used to analyze the expression distribution of hub genes and cell–cell communications. Finally, we collected human blood samples for RT-qPCR and Elisa experiments, the miRNA-mRNA network was constructed using the miRBase database, the 3D structure was predicted using the RNAfold, Vfold3D database, and the drug sensitivity analysis was performed using the RNAactDrug database. We obtained three differentially expressed genes associated with oxidative stress: DBH, TAF15, and STAT4 by differential, WGCNA clustering, and Venn screening analyses, and further analyzed the correlation of these 3 genes with inflammatory factors and immune cell infiltration and found that STAT4 was significantly and positively correlated with IL-2. Single-cell data analysis showed that the STAT4 gene was highly expressed mainly in dendritic cells and monocytes. In addition, the results of RT-qPCR and Elisa experiments verified that the expression of STAT4 was consistent with the previous analysis, and a significant causal relationship between IL-2 and STAT4 SNPs and osteoporosis was found by Mendelian randomization. Finally, through miRNA-mRNA network and drug sensitivity analysis, we analyzed to get Palbociclib/miR-141-3p/STAT4 axis, which can be used for the prevention and treatment of osteoporosis. In this study, we proposed the Palbociclib/miR-141-3p/STAT4 axis for the first time and provided new insights into the mechanism of oxidative stress in osteoporosis.

骨质疏松症是一种常见的骨病，其特征是骨量减少、骨强度降低和骨微结构恶化。ROS诱导的氧化应激在骨质疏松症中起着重要作用。然而，氧化应激的生物标志物和分子机制仍不清楚。我们从基因表达综合（GEO）数据库中获取数据集，并对中心基因进行差异分析、维恩分析和加权相关网络分析（WGCNA）分析。然后，分析炎症因子和枢纽基因之间的相关性，并对细胞因子和骨质疏松症结果进行孟德尔随机化（MR）分析。此外，“CIBERSORT”用于分析免疫细胞的浸润情况，单细胞RNA-seq数据用于分析中枢基因的表达分布和细胞间通讯。最后，我们收集人体血液样本进行RT-qPCR和Elisa实验，利用miRBase数据库构建miRNA-mRNA网络，利用RNAfold、Vfold3D数据库预测3D结构，利用RNAactDrug数据库进行药物敏感性分析。我们通过差异分析、WGCNA聚类和维恩筛选分析获得了3个与氧化应激相关的差异表达基因：DBH、TAF15和STAT4，并进一步分析了这3个基因与炎症因子和免疫细胞浸润的相关性，发现STAT4显着且与IL-2呈正相关。单细胞数据分析显示STAT4基因主要在树突状细胞和单核细胞中高表达。此外，RT-qPCR和Elisa实验的结果验证了STAT4的表达与之前的分析一致，并且通过孟德尔随机化发现IL-2和STAT4 SNP与骨质疏松之间存在显着的因果关系。最后，通过miRNA-mRNA网络和药物敏感性分析，我们分析得到Palbociclib/miR-141-3p/STAT4轴，可用于骨质疏松症的预防和治疗。在本研究中，我们首次提出Palbociclib/miR-141-3p/STAT4轴，为骨质疏松中氧化应激的机制提供了新的见解。