Department of Cardiology, Gansu Provincial Hospital, Lanzhou, 730000, China.
Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, 200062, China.
Hum Genomics. 2019 Aug 29;13(1):40. doi: 10.1186/s40246-019-0232-4.
Understanding the roles of miRNAs in cardiovascular disease remains a challenge. Genomic linkage indicates a functional relationship between intronic miRNAs and their host genes. However, few studies have shown functional association between intronic miRNAs and their host coding genes that are genetically associated with cardiovascular disease.
In this study, we investigated functional relationship between three protein-coding genes genetically associated with cardiovascular disease, i.e., CDH13, SLC12A3, and CKAP5, and their intronic miRNAs using a data-driven approach.
We found that the three protein-coding genes functionally interact with targets of their intronic miRNAs, i.e., miR-3182, miR-6863, and miR-5582, in a tissue-specific pattern. The intronic miRNAs preferentially impact important genes for the three host genes in the network, indicating their roles in maintaining the integrity of the interactome where the host genes are involved. Targets of the intronic miRNAs display functional similarity to the host genes. We furthermore present sets of target genes for future investigation on the possible miRNA-target interactions that potentially contribute to cardiovascular diseases.
Our work provides new insight into the regulatory network of the cardiovascular-associated pathways and opens the possibility for future experimental research.
理解 miRNA 在心血管疾病中的作用仍然是一个挑战。基因组连锁表明内含子 miRNA 与其宿主基因之间存在功能关系。然而，很少有研究表明与心血管疾病遗传相关的内含子 miRNA 与其宿主编码基因之间存在功能关联。
在这项研究中，我们使用数据驱动的方法研究了与心血管疾病相关的三个蛋白质编码基因，即 CDH13、SLC12A3 和 CKAP5 及其内含子 miRNA 之间的功能关系。
我们发现，这三个蛋白质编码基因以组织特异性的方式与它们内含子 miRNA 的靶标，即 miR-3182、miR-6863 和 miR-5582，相互作用。内含子 miRNA 优先影响网络中三个宿主基因的重要基因，表明它们在维持宿主基因参与的相互作用组的完整性方面发挥作用。内含子 miRNA 的靶标与宿主基因具有功能相似性。我们还提出了一组靶基因，以供未来对可能导致心血管疾病的 miRNA-靶标相互作用的研究。
我们的工作为心血管相关途径的调控网络提供了新的见解，并为未来的实验研究开辟了可能性。
