构建骨关节炎的竞争性内源性RNA网络。
Constructing a competing endogenous RNA network for osteoarthritis.
作者信息
Hua Shu-Liang, Liang Jun-Qing, Hu Guo-Fang, Yang Xi-Ren, Fang Da-Lang, Lu Ji-Li
机构信息
Department of Bone and Joint Surgery, the People's Hospital of Baise, Baise, China.
Department of Breast and Thyroid Surgery, the Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.
出版信息
Ann Transl Med. 2022 Feb;10(3):147. doi: 10.21037/atm-21-6711.
BACKGROUND
Osteoarthritis (OA) is one of the most common diseases in elderly people; however, the correlation between molecular alterations and the occurrence and progression of OA are still not well understood. We conducted this study to investigate the molecular changes in OA via the competing endogenous ribonucleic acid (ceRNA) network.
METHODS
We downloaded the messenger RNA (mRNA) data set, GSE48556, the microRNA (miRNA) data set, GSE105027, and the long non-coding (lncRNA) data set, GSE126963 from the Gene Expression Omnibus (GEO) database, and examined the differentially expressed genes (DEGs) in these data sets. Further, we constructed a ceRNA network of the differentially expressed miRNAs, mRNAs, and lncRNAs. To determine the biological functions of the ceRNA network, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses. Finally, we conducted an immune cell infiltration analysisusing single-sample gene set enrichment analysis to examine the abundance of immune cells in healthy and OA patients, and compared the infiltration of 28 immune cells between the healthy and OA samples. We also analyzed the relationship between the abundance of immune cells and mRNA expression levels in the ceRNA network.
RESULTS
Ultimately hsa-mir-425-3p, dual specificity phosphatase 1, and 24 lncRNAs were identified in the ceRNA network. The functional enrichment analyses showed that these lncRNAs, miRNAs, and mRNAs are involved in various significant biological process, such as the regulation of leukocyte migration, Mitogen-Activated Protein (MAP) kinase tyrosine/serine/threonine phosphatase activity, the interleukin-17 signaling pathway, the tumor necrosis factor signaling pathway, and osteoclast differentiation, and can also have a strong effect on immune cell infiltration.
CONCLUSIONS
The dual-specificity phosphatase 1-specific ceRNA network can be used as a diagnostic tool to assess the progression of OA patients.
背景
骨关节炎（OA）是老年人中最常见的疾病之一；然而，分子改变与OA发生和进展之间的相关性仍未得到充分理解。我们开展本研究以通过竞争性内源性核糖核酸（ceRNA）网络研究OA中的分子变化。
方法
我们从基因表达综合数据库（GEO）下载了信使核糖核酸（mRNA）数据集GSE48556、微小核糖核酸（miRNA）数据集GSE105027和长链非编码核糖核酸（lncRNA）数据集GSE126963，并检查了这些数据集中的差异表达基因（DEG）。此外，我们构建了差异表达的miRNA、mRNA和lncRNA的ceRNA网络。为确定ceRNA网络的生物学功能，我们进行了基因本体（GO）和京都基因与基因组百科全书（KEGG）功能富集分析。最后，我们使用单样本基因集富集分析进行免疫细胞浸润分析，以检查健康人和OA患者中免疫细胞的丰度，并比较健康样本和OA样本之间28种免疫细胞的浸润情况。我们还分析了ceRNA网络中免疫细胞丰度与mRNA表达水平之间的关系。
结果
最终在ceRNA网络中鉴定出hsa-mir-425-3p、双特异性磷酸酶1和24种lncRNA。功能富集分析表明，这些lncRNA、miRNA和mRNA参与各种重要的生物学过程，如白细胞迁移调节、丝裂原活化蛋白（MAP）激酶酪氨酸/丝氨酸/苏氨酸磷酸酶活性、白细胞介素-17信号通路、肿瘤坏死因子信号通路和破骨细胞分化，并且对免疫细胞浸润也有强烈影响。
结论
双特异性磷酸酶1特异性ceRNA网络可作为评估OA患者病情进展的诊断工具。
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