Department of Anatomy, Biochemistry, and Physiology, John A. Burns School of Medicine, The University of Hawaii at Manoa, Honolulu, HI, 96813, USA.
Department of Animal Science and Aquaculture, Dalhousie University, Truro, Nova Scotia, Canada.
Comput Biol Med. 2022 Oct;149:105996. doi: 10.1016/j.compbiomed.2022.105996. Epub 2022 Aug 27.
Recently, Inflammatory Bowel Disease (IBD) has been proven as a risk factor for the increasing incidence of cervical cancer (CC) development. In this study, we identify these potential hub genes and their significant pathways that commonly interact between IBD and CC and these pathological mechanisms. To this end, we use bioinformatics and systems biology approaches to analyze the miRNA-mRNA, TFs-mRNA regulatory network.
The reanalysis dataset from Gene Expression Omnibus (GEO) and the cancer genome atlas (TCGA) found these common differentially expressed genes (DEGs) between IBD and CC, clustered via weighted gene co-expression network analysis, and the vital modules significantly related to cervical cancer were identified. These hub genes of the key module were identified and explored in biological mechanism pathway analysis. Organelle fission, nuclear envelope, protein serine/threonine kinase activity, and the Human T-cell leukemia virus 1 infection pathway were the major enriched pathways for the common DEGs. Due to the high connectivity, the common DEGs with protein-protein interaction (PPI) network disclosed hub proteins (CDK1, MAD2L1, and CCNB1). This study also showed the classification algorithms of ten hub genes (MAD2L1, CCNB2, CDK1, CCNA2, BUB1B, KIF11, TTK, BUB1, CCNB1, ASPM) with accuracy >0.90 suggesting the novel biomarker potential of the hub genes. The microRNAs (miRNA), and transcription factors (TFs) mRNA regulatory network, five transcription factors, and twelve miRNAs are strongly linked to three hub genes. Gene drug interaction analysis found seven drugs compound that interacts with the hub gene.
In the current study, our procedure has hypothesized the comprehensive understanding of disease mechanisms vital for both CC and IBD that may mediate their interaction. Our results suggest the further investigation of the molecules for the treatment of IBD and CC.
最近，炎症性肠病（IBD）已被证明是宫颈癌（CC）发展发病率增加的一个风险因素。在这项研究中，我们确定了这些潜在的枢纽基因及其在 IBD 和 CC 之间共同作用的重要途径以及这些病理机制。为此，我们使用生物信息学和系统生物学方法来分析 miRNA-mRNA、TFs-mRNA 调控网络。
从基因表达综合数据库（GEO）和癌症基因组图谱（TCGA）重新分析数据集，发现 IBD 和 CC 之间存在这些常见的差异表达基因（DEGs），通过加权基因共表达网络分析进行聚类，并确定与宫颈癌显著相关的重要模块。识别关键模块的枢纽基因，并在生物学机制途径分析中进行探索。细胞器分裂、核包膜、蛋白丝氨酸/苏氨酸激酶活性和人类 T 细胞白血病病毒 1 感染途径是常见 DEGs 的主要富集途径。由于高度连接性，具有蛋白质-蛋白质相互作用（PPI）网络的常见 DEGs 揭示了枢纽蛋白（CDK1、MAD2L1 和 CCNB1）。该研究还显示了十个枢纽基因（MAD2L1、CCNB2、CDK1、CCNA2、BUB1B、KIF11、TTK、BUB1、CCNB1 和 ASPM）的分类算法准确率>0.90，提示这些枢纽基因具有潜在的新型生物标志物。miRNA 和转录因子（TFs）mRNA 调控网络，五个转录因子和十二个 miRNAs 与三个枢纽基因强烈相关。基因药物相互作用分析发现七种与枢纽基因相互作用的药物化合物。
在目前的研究中，我们的方法假设对 CC 和 IBD 都至关重要的疾病机制有全面的了解，这可能介导它们的相互作用。我们的结果提示进一步研究这些分子用于治疗 IBD 和 CC。
