Department of Respirology, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China.
School of Biotechnology, East China University of Science and Technology, Shanghai 200237, China.
Infect Genet Evol. 2020 Sep;83:104323. doi: 10.1016/j.meegid.2020.104323. Epub 2020 Apr 16.
Circular RNAs (circRNAs) are known to be closely involved in various diseases progression. Nevertheless, their function and underlying mechanisms in tuberculosis (TB) remain largely unknown. The aim of the present study was to explore their potential diagnostic values in TB. We downloaded the gene expression datasets of circRNA (GSE117563 and GSE106953), microRNA (miRNA, dataset GSE29190) and mRNA (GSE54992) from Gene Expression Omnibus (GEO) database. A competing endogenous RNAs (ceRNA) network was constructed based on circRNA-miRNA-mRNA potential interaction. We also constructed a circRNA-miRNA-hub gene regulatory module by using the Cytohubba. Gene ontology (GO) as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to predict their biological functions. By further validation, the expression level of hsa_circ_0028883 and hsa-miR-409-5p were detected by qRT-PCR in 20 active TB patients and 20 healthy donors. Then, Receiver Operating Characteristic (ROC) was constructed to evaluate the diagnostic values of hsa_circ_0028883. 1 differentially expressed circRNA (DE-circRNA), 1 differentially expressed miRNA (DE-miRNA), and 44 differentially expressed mRNAs (DE-mRNAs) were selected for the construction of ceRNA network in TB. A circRNA-miRNA-hub gene (mRNA) sub-network was constructed based on 1 DE-circRNA, 1 DE-miRNA, and 8 DE-mRNAs. Hsa_circ_0028883/hsa-miR-409-5p/mRNA interactions may provide some novel mechanisms for active TB. GO and KEGG pathway analysis indicated the possible function of hsa_circ_0028883 with TB. ROC analysis revealed that hsa_circ_0028883 had potential value for TB diagnosis. Hsa_circ_0028883 is a potentially reliable biomarker to diagnose active TB, but there remains a need to further study the mechanism in TB.
环状 RNA（circRNA）被认为与多种疾病的进展密切相关。然而，它们在结核病（TB）中的功能和潜在机制在很大程度上仍不清楚。本研究旨在探讨其在 TB 中的潜在诊断价值。我们从基因表达数据库（GEO）下载了环状 RNA（circRNA，数据集 GSE117563 和 GSE106953）、microRNA（miRNA，数据集 GSE29190）和 mRNA（GSE54992）的基因表达数据集。基于 circRNA-miRNA-mRNA 潜在相互作用构建竞争性内源 RNA（ceRNA）网络。我们还使用 Cytohubba 构建了环状 RNA-miRNA-枢纽基因调控模块。基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路分析用于预测它们的生物学功能。通过进一步验证，我们使用 qRT-PCR 在 20 名活动性 TB 患者和 20 名健康供体中检测了 hsa_circ_0028883 和 hsa-miR-409-5p 的表达水平。然后，构建接收者操作特征（ROC）曲线以评估 hsa_circ_0028883 的诊断价值。在 TB 中构建 ceRNA 网络时，选择了 1 个差异表达的环状 RNA（DE-circRNA）、1 个差异表达的 miRNA（DE-miRNA）和 44 个差异表达的 mRNAs（DE-mRNAs）。基于 1 个 DE-circRNA、1 个 DE-miRNA 和 8 个 DE-mRNAs，构建了环状 RNA-miRNA-枢纽基因（mRNA）子网络。Hsa_circ_0028883/hsa-miR-409-5p/mRNA 相互作用可能为活动性 TB 提供一些新的机制。GO 和 KEGG 通路分析表明 hsa_circ_0028883 与 TB 可能存在功能联系。ROC 分析表明 hsa_circ_0028883 对 TB 诊断具有潜在价值。Hsa_circ_0028883 是诊断活动性 TB 的一种潜在可靠生物标志物，但仍需要进一步研究 TB 中的机制。
