雜志名稱：Scientific Reports
影響因子：4.6
文章題目：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
作者單位：
西安交通大學(xué)弘輝醫(yī)院脊柱外科；
西安交通大學(xué)附屬醫(yī)院；
香港賽馬會獸醫(yī)學(xué)院傳染病及公共衛(wèi)生學(xué)系；
香港城市大學(xué)生命科學(xué)學(xué)院，中國香港第一轉(zhuǎn)化醫(yī)學(xué)中心
引用產(chǎn)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.
骨質(zhì)疏松癥是一種常見的骨病，其特征是骨量減少、骨強度降低和骨微結(jié)構(gòu)惡化。ROS誘導(dǎo)的氧化應(yīng)激在骨質(zhì)疏松癥中起著重要作用。然而，氧化應(yīng)激的生物標(biāo)志物和分子機制仍不清楚。我們從基因表達(dá)綜合（GEO）數(shù)據(jù)庫中獲取數(shù)據(jù)集，并對中心基因進行差異分析、維恩分析和加權(quán)相關(guān)網(wǎng)絡(luò)分析（WGCNA）分析。然后，分析炎癥因子和樞紐基因之間的相關(guān)性，并對細(xì)胞因子和骨質(zhì)疏松癥結(jié)果進行孟德爾隨機化（MR）分析。此外，“CIBERSORT”用于分析免疫細(xì)胞的浸潤情況，單細(xì)胞RNA-seq數(shù)據(jù)用于分析中樞基因的表達(dá)分布和細(xì)胞間通訊。最后，我們收集人體血液樣本進行RT-qPCR和Elisa實驗，利用miRBase數(shù)據(jù)庫構(gòu)建miRNA-mRNA網(wǎng)絡(luò)，利用RNAfold、Vfold3D數(shù)據(jù)庫預(yù)測3D結(jié)構(gòu)，利用RNAactDrug數(shù)據(jù)庫進行藥物敏感性分析。我們通過差異分析、WGCNA聚類和維恩篩選分析獲得了3個與氧化應(yīng)激相關(guān)的差異表達(dá)基因：DBH、TAF15和STAT4，并進一步分析了這3個基因與炎癥因子和免疫細(xì)胞浸潤的相關(guān)性，發(fā)現(xiàn)STAT4顯著且與IL-2呈正相關(guān)。單細(xì)胞數(shù)據(jù)分析顯示STAT4基因主要在樹突狀細(xì)胞和單核細(xì)胞中高表達(dá)。此外，RT-qPCR和Elisa實驗的結(jié)果驗證了STAT4的表達(dá)與之前的分析一致，并且通過孟德爾隨機化發(fā)現(xiàn)IL-2和STAT4 SNP與骨質(zhì)疏松之間存在顯著的因果關(guān)系。最后，通過miRNA-mRNA網(wǎng)絡(luò)和藥物敏感性分析，我們分析得到Palbociclib/miR-141-3p/STAT4軸，可用于骨質(zhì)疏松癥的預(yù)防和治療。在本研究中，我們首次提出Palbociclib/miR-141-3p/STAT4軸，為骨質(zhì)疏松中氧化應(yīng)激的機制提供了新的見解。
