School of Medicine, Marmara University, Istanbul, Türkiye.
Department of Bioengineering, Faculty of Engineering, Marmara University, Istanbul, Türkiye.
OMICS. 2023 Aug;27(8):381-392. doi: 10.1089/omi.2023.0072. Epub 2023 Aug 4.
Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrotic disease of the lung with poor prognosis. Fibrosis results from remodeling of the interstitial tissue. A wide range of gene expression changes are observed, but the role of micro RNAs (miRNAs) and circular RNAs (circRNA) is still unclear. Therefore, this study aimed to establish an messenger RNA (mRNA)-miRNA-circRNA competing endogenous RNA (ceRNA) regulatory network to uncover novel molecular signatures using systems biology tools. Six datasets were used to determine differentially expressed genes (DEGs) and miRNAs (DEmiRNA). Accordingly, protein-protein, mRNA-miRNA, and miRNA-circRNA interactions were constructed. Modules were determined and further analyzed in the Drug Gene Budger platform to identify potential therapeutic compounds. We uncovered common 724 DEGs and 278 DEmiRNAs. In the protein-protein interaction network, , , , , and were identified as hub protein coding genes. The mRNA-miRNA interaction network revealed two modules composed of , , hsa-miR-484 and , , and hsa-miR-543. The DEmiRNAs in the modules further analyzed to propose potential circRNA regulators in the ceRNA network. These results help deepen the understanding of the mechanisms of IPF. In addition, the molecular leads reported herein might inform future innovations in diagnostics and therapeutics research and development for IPF.
特发性肺纤维化(IPF)是一种预后不良的慢性进行性肺纤维化疾病。纤维化是由间质组织重塑引起的。观察到广泛的基因表达变化,但 microRNAs(miRNAs)和 circular RNAs(circRNAs)的作用仍不清楚。因此,本研究旨在使用系统生物学工具建立信使 RNA(mRNA)-miRNA-circRNA 竞争内源性 RNA(ceRNA)调控网络,以揭示新的分子特征。使用六个数据集来确定差异表达基因(DEGs)和 microRNAs(DEmiRNA)。相应地,构建了蛋白质-蛋白质、mRNA-miRNA 和 miRNA-circRNA 相互作用。在 Drug Gene Budger 平台上确定模块并进一步分析,以识别潜在的治疗化合物。我们发现了 724 个共同的 DEGs 和 278 个 DEmiRNAs。在蛋白质-蛋白质相互作用网络中, 、 、 、 、 被鉴定为枢纽蛋白编码基因。在 mRNA-miRNA 相互作用网络中,揭示了由 、 、 hsa-miR-484 和 、 、 hsa-miR-543 组成的两个模块。进一步分析模块中的 DEmiRNAs,提出 ceRNA 网络中潜在的 circRNA 调节剂。这些结果有助于加深对 IPF 机制的理解。此外,本文报道的分子线索可能为未来 IPF 的诊断和治疗研究与开发提供新的创新。