Chronic obstructive pulmonary disease (COPD) is a global high-incidence chronic airway inflammation disease. Its deterioration will lead to more serious lung lesions and even lung cancer. Therefore, it is urgent to determine the pathogenesis of COPD and find potential therapeutic targets. The purpose of this study is to reveal the molecular mechanism of COPD disease development through in-depth analysis of transcription factors and ncRNA-driven pathogenic modules of COPD. We obtained the expression profile of COPD-related microRNAs from the NCBI-GEO database and analyzed the differences among groups to identify the microRNAs significantly associated with COPD. Then, their target genes are predicted and mapped to a protein-protein interaction (PPI) network. Finally, key transcription factors and the ncRNA of the regulatory module were identified based on the hypergeometric test. The results showed that CUL1 was the most interactive gene in the highly interactive module, so it was recognized as a dysfunctional molecule of COPD. Enrichment analysis also showed that it was much involved in the biological process of organelle fission, the highest number of regulatory modules. In addition, ncRNAs, mainly composed of miR-590-3p, miR-495-3p, miR-186-5p, and transcription factors such as MYC, BRCA1, and CDX2, significantly regulate COPD dysfunction blocks. In summary, we revealed that the COPD-related target gene CUL1 plays a key role in the potential dysfunction of the disease. It promotes the proliferation of fibroblast cells in COPD patients by mediating functional signals of organelle fission and thus participates in the progress of the disease. Our research helps biologists to further understand the etiology and development trend of COPD.

中文翻译：

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CUL1介导的细胞器裂变途径抑制了慢性阻塞性肺疾病的发展。

慢性阻塞性肺疾病（COPD）是一种全球性高发病率慢性气道炎症疾病。其恶化将导致更严重的肺部病变，甚至肺癌。因此，迫切需要确定COPD的发病机制并寻找潜在的治疗靶点。本研究的目的是通过深入分析COPD的转录因子和ncRNA驱动的致病模块，揭示COPD疾病发展的分子机制。我们从NCBI-GEO数据库获得了COPD相关microRNA的表达谱，并分析了各组之间的差异以鉴定与COPD显着相关的microRNA。然后，预测其靶基因并将其定位到蛋白质-蛋白质相互作用（PPI）网络。最后，基于超几何检验，确定了关键的转录因子和调控模块的ncRNA。结果表明，CUL1是高度相互作用模块中相互作用最强的基因，因此被认为是COPD功能障碍的分子。富集分析还表明，它参与了细胞器裂变的生物过程，是调节模块数量最多的过程。此外，主要由miR-590-3p，miR-495-3p，miR-186-5p和MYC，BRCA1和CDX2等转录因子组成的ncRNA显着调节了COPD功能障碍。总而言之，我们揭示了COPD相关靶基因CUL1在该疾病的潜在功能障碍中起关键作用。它通过介导细胞器裂变的功能信号来促进COPD患者的成纤维细胞增殖，从而参与疾病的发展。我们的研究有助于生物学家进一步了解COPD的病因和发展趋势。