Background: Revealing the process and mechanism of colorectal cancer will facilitate the discovery of new biomarkers and contribute to the development of targeted drugs. Objective: This study aimed to explore the potentially functional circRNA-miRNA-mRNA network in colorectal cancer (CRC), and further explore its mechanism. Methods: Bioinformatics analysis was used to identify the differentially expressed circRNAs and mRNAs. Gene set enrichment analysis and KEGG pathways analysis were used to screen out the differentially expressed genes and observe crucial pathways that might have a strong association with CRC. Then, a network targeting circRNA, miRNA, and mRNA has been built by using the Cytoscape software. In addition, the expression of circRNA_0001573, miR-382-5p, and FZD3 was detected by qRT-PCR in CRC tissues and cells (SW480, HCT116, and HT29). Results: Abnormal expressions of circRNAs and mRNAs were obtained by bioinformatics analysis and visualized by Volcano plot and Heatmap. A series of highly correlated pathways were enriched by KEGG analysis. The interaction network of circRNA_0001573/miR-382-5p/FZD3 axis was predicted. The expressions of circRNA_0001573 and FZD3 were highly upregulated and the miR- 382-5p expression level was decreased in CRC tissues and cell lines (SW480, HCT116, and HT29). Conclusion: Our study suggests that circRNA_0001573 and circRNA_0001573/miR-382-5p/FZD3 regulatory networks might provide a potential diagnosis for colorectal cancer.

中文翻译：

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circRNA-miRNA-mRNA 调控网络在结直肠癌中的作用及其潜在生物标志物功能


背景：揭示结直肠癌的发生过程和机制将有助于新生物标志物的发现，并有助于靶向药物的开发。目的：本研究旨在探讨结直肠癌（CRC）中潜在的功能性circRNA-miRNA-mRNA网络，并进一步探讨其机制。方法：采用生物信息学分析鉴定差异表达的circRNA和mRNA。采用基因集富集分析和KEGG通路分析筛选差异表达基因，观察可能与CRC密切相关的关键通路。然后，使用 Cytoscape 软件构建了针对 circRNA、miRNA 和 mRNA 的网络。此外，通过qRT-PCR检测CRC组织和细胞（SW480、HCT116和HT29）中circRNA_0001573、miR-382-5p和FZD3的表达。结果：通过生物信息学分析获得circRNA和mRNA的异常表达，并通过火山图和热图可视化。通过KEGG分析丰富了一系列高度相关的通路。预测了circRNA_0001573/miR-382-5p/FZD3轴的相互作用网络。在CRC组织和细胞系（SW480、HCT116和HT29）中，circRNA_0001573和FZD3的表达高度上调，而miR-382-5p表达水平降低。结论：我们的研究表明，circRNA_0001573 和 circRNA_0001573/miR-382-5p/FZD3 调控网络可能为结直肠癌提供潜在的诊断。