Li Wentao, Wei Jinmei, Huang Pingping, Wei Yuhui, Chang Li, Liu Guangnan
Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Guangxi Medical University, Nanning, China.
Guangxi Medical University, Nanning, China.
Front Genet. 2024 Jan 8;14:1291488. doi: 10.3389/fgene.2023.1291488. eCollection 2023.
Traumatic tracheal stenosis (TTS) is a major cause of complex difficult airways, without clinically definitive efficacious drugs available. The aim of this study was to provide a general view of interactions between micro and messenger ribonucleic acids (miRNAs and mRNAs) and many potential mechanisms in TTS small RNA sequencing. In this study, the identification of miRNAs was completed using small RNA sequencing and samples from four TTS patients and four normal control cases. By using bioinformatics tools, such as miRanda and RNAhybrid, for identifying the candidate target genes of miRNAs with differential expression in each sample, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were employed for enriching the predicted target genes of miRNAs with differential expression based on the correspondence between miRNAs and their target genes. We detected the expression of the candidate miRNAs using quantitative real-time polymerase chain reaction (qRT-PCR). Twenty-four miRNAs with significant differential expression were identified, including 13 upregulated and 11 downregulated ones. Bioinformation technology was adopted to predict 2,496 target genes. These miRNA-target genes were shown to be primarily enriched in cells and organelles with catalytic activity and binding function, such as binding proteins, small molecules, and nucleotides. Finally, they were observed to process into TTS through the intercellular and signal regulation of related inflammatory signaling and fibrosis signaling pathways. QRT-PCR confirmed the upregulation of miR21-5p and miR214-3p and the downregulation of miR141-3p and miR29b-3p, which was expected to become a high-specific miRNA for TTS. Among all the miRNAs detected, 24 miRNAs demonstrated differential expression between the TTS and normal control groups. A total of 2,496 target genes were predicted by bioinformation technology and enriched in inflammatory and fibrotic signaling pathways. These results provide new ideas for further studies and the selection of targets for TTS in the future.
创伤性气管狭窄(TTS)是导致复杂困难气道的主要原因,目前尚无临床明确有效的药物。本研究旨在全面了解微小核糖核酸(miRNA)与信使核糖核酸(mRNA)之间的相互作用以及TTS中小RNA测序中的许多潜在机制。在本研究中,使用小RNA测序技术对4例TTS患者和4例正常对照病例的样本进行miRNA鉴定。通过使用诸如miRanda和RNAhybrid等生物信息学工具来鉴定每个样本中差异表达的miRNA的候选靶基因,并基于miRNA与其靶基因的对应关系,利用基因本体论(Gene Ontology)和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes)对差异表达的miRNA的预测靶基因进行富集分析。我们使用定量实时聚合酶链反应(qRT-PCR)检测候选miRNA的表达。共鉴定出24个差异表达显著的miRNA,其中13个上调,11个下调。采用生物信息技术预测出2496个靶基因。这些miRNA靶基因主要富集于具有催化活性和结合功能的细胞和细胞器中,如结合蛋白、小分子和核苷酸。最后观察到它们通过相关炎症信号通路和纤维化信号通路的细胞间和信号调节作用参与TTS的发生发展。qRT-PCR证实了miR21-5p和miR214-3p的上调以及miR141-3p和miR29b-3p的下调,有望成为TTS的高特异性miRNA。在所有检测到的miRNA中,有24个在TTS组和正常对照组之间表现出差异表达。通过生物信息技术共预测出2496个靶基因,并富集于炎症和纤维化信号通路中。这些结果为未来TTS的进一步研究和靶点选择提供了新思路。