ABSTRACT

Background: The dysregulation of renin-angiotensin-aldosterone system (RAAS) is closely related to the development of essential hypertension (EH). MicroRNAs (miRNAs) are an important regulator of RAAS. The sponge effect of circular RNAs (circRNAs) on miRNAs makes the circRNA-miRNA-mRNA axis in EH possible, however, there is currently a lack of relevant evidence.

Material and Methods: A circRNA-miRNA network was constructed based on the previous circRNAs microarray results. The expression of RAAS-related miRNAs and circRNAs were verified by qRT-PCR. Peripheral blood samples of 106 EH patients and 106 healthy volunteers were included in this study. GO and KEGG enrichment were performed to predict the role of candidate circRNAs in EH.

Results: In EH patients, RAAS-related hsa-miR-483-3p and hsa-miR-27a-3p were down-regulated, and hsa_circ_0122153 and hsa_circ_0025088 were up-regulated. The relative expression of RAAS-related circRNAs and target miRNAs showed a negative correlation (hsa_circ_0122153-hsa-miR-483-3p and hsa_circ_0025088-hsa-miR-27a-3p). Hsa_circ_0122153 or hsa_circ_0025088 combined with corresponding miRNAs and environmental factors may support the early diagnosis of EH. Hsa_circ_0122153 and hsa_circ_0025088 may participate in the regulation of aldosterone and the secretion of renin through the circRNA-miRNA-mRNA network, respectively.

Conclusion: Highly expressed hsa_circ_0122153 and hsa_circ_0025088 increase the risk of EH. The hsa_circ_0122153/hsa-miR-483-3p and hsa_circ_0025088/hsa-miR-27a-3p axis involving RAAS were potential EH pathways.

摘要

背景：肾素-血管紧张素-醛固酮系统（RAAS）的失调与原发性高血压（EH）的发生密切相关。MicroRNAs (miRNAs) 是 RAAS 的重要调节因子。环状RNA（circRNA）对miRNA的海绵效应使EH中的circRNA-miRNA-mRNA轴成为可能，但目前缺乏相关证据。

材料与方法：基于先前的circRNA微阵列结果构建了circRNA-miRNA网络。通过qRT-PCR验证RAAS相关miRNA和circRNA的表达。本研究包括 106 名 EH 患者和 106 名健康志愿者的外周血样本。进行 GO 和 KEGG 富集以预测候选 circRNA 在 EH 中的作用。

结果：在EH患者中，RAAS相关的hsa-miR-483-3p和hsa-miR-27a-3p下调，hsa_circ_0122153和hsa_circ_0025088上调。RAAS相关的circRNA和靶miRNA的相对表达呈负相关（hsa_circ_0122153-hsa-miR-483-3p和hsa_circ_0025088-hsa-miR-27a-3p）。Hsa_circ_0122153或hsa_circ_0025088结合相应的miRNA和环境因素可能支持EH的早期诊断。Hsa_circ_0122153和hsa_circ_0025088可能分别通过circRNA-miRNA-mRNA网络参与醛固酮的调节和肾素的分泌。

结论：高表达的 hsa_circ_0122153 和 hsa_circ_0025088 会增加 EH 的风险。涉及 RAAS 的 hsa_circ_0122153/hsa-miR-483-3p 和 hsa_circ_0025088/hsa-miR-27a-3p 轴是潜在的 EH 通路。