微阵列鉴定环状 RNA hsa_circ_0105015 在原发性高血压中涉及炎症通路的上调。
The microarray identification circular RNA hsa_circ_0105015 up-regulated involving inflammation pathway in essential hypertension.
机构信息
Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, Medical School of Ningbo University, Ningbo, China.
Department of Public health, Ningbo Seventh Hosptial, Ningbo, China.
出版信息
J Clin Lab Anal. 2021 Feb;35(2):e23603. doi: 10.1002/jcla.23603. Epub 2020 Nov 24.
BACKGROUND
Essential hypertension (EH) is an inflammatory disease, and endothelial dysfunction induced by chronic inflammation is one of the pathogeneses of EH. The expression of some inflammatory mediators may be regulated by the interaction of circular RNAs (circRNAs) and microRNAs (miRNAs).
METHODS
An Agilent human circRNA microarray was used to identify the expression profile of circRNAs in EH. qRT-PCR was used to evaluate the relative expression of circRNAs in 48 pairs of human whole blood samples (sex and age ± 3 years matched) and endothelial cells. TNF-α was applied to induce endothelial cells inflammation. CircRNA-miRNA network was predicted by MiRanda software.
RESULTS
There were 287 circRNAs differentially expressed in the microarray. The top 10 up-regulated circRNAs in the EH group were hsa_circ_0014243, hsa_circ_0133228, hsa-circRNA14116-3, hsa_circ_0079536, hsa-circRNA13649-1, hsa_circ_0117886, hsa_circ_0007075, hsa-circRNA15285-1, hsa-circRNA10088-9, and hsa-circRNA14119-10; the top 10 down-regulated circRNAs were hsa_circ_0100094, hsa_circ_0127342, hsa_circ_0093773, hsa_circ_0096334, hsa_circ_0131618, hsa_circ_0063886, hsa_circ_0097804, hsa_circ_0126640, hsa-circRNA8935-1, and hsa_circ_0039978 (fold change in descending order). Hsa_circ_0105015 has two predicted binding sites with hsa-miR-637. The relative expression of hsa_circ_0105015 in EH patients was significantly higher than healthy controls (P = .002), and similar results appeared in TNF-α-induced endothelial cells. The area under the curve after hsa_circ_0105015 combined with hsa-miR-637 was 0.703, P < .001.
CONCLUSION
Hyperexpression of hsa_circ_0105015 is a significant risk factor of EH and its association with EH involves inflammatory pathways. Hyperexpression of hsa_circ_0105015 combined with hypoexpression of hsa-miR-637 indicates vascular inflammation or endothelial dysfunction and has potential as a biomarker for early diagnosis of EH.
背景
原发性高血压（EH）是一种炎症性疾病，慢性炎症引起的内皮功能障碍是 EH 的发病机制之一。一些炎症介质的表达可能受到环状 RNA（circRNA）和 microRNA（miRNA）相互作用的调节。
方法
采用 Agilent 人 circRNA 微阵列鉴定 EH 中 circRNA 的表达谱。qRT-PCR 用于评估 48 对人全血样本（性别和年龄相差 3 岁）和内皮细胞中 circRNA 的相对表达。应用 TNF-α诱导内皮细胞炎症。利用 MiRanda 软件预测 circRNA-miRNA 网络。
结果
微阵列中差异表达的 circRNA 有 287 个。EH 组中上调的前 10 个 circRNA 为 hsa_circ_0014243、hsa_circ_0133228、hsa-circRNA14116-3、hsa_circ_0079536、hsa-circRNA13649-1、hsa_circ_0117886、hsa_circ_0007075、hsa-circRNA15285-1、hsa-circRNA10088-9 和 hsa-circRNA14119-10；下调的前 10 个 circRNA 为 hsa_circ_0100094、hsa_circ_0127342、hsa_circ_0093773、hsa_circ_0096334、hsa_circ_0131618、hsa_circ_0063886、hsa_circ_0097804、hsa_circ_0126640、hsa-circRNA8935-1 和 hsa_circ_0039978（按降序排列）。hsa_circ_0105015 有两个与 hsa-miR-637 结合的预测位点。EH 患者 hsa_circ_0105015 的相对表达水平明显高于健康对照组（P=0.002），在 TNF-α诱导的内皮细胞中也出现了类似的结果。hsa_circ_0105015 与 hsa-miR-637 联合后的曲线下面积为 0.703，P<0.001。
结论
hsa_circ_0105015 的高表达是 EH 的一个显著危险因素，其与 EH 的关联涉及炎症途径。hsa_circ_0105015 的高表达与 hsa-miR-637 的低表达相结合提示血管炎症或内皮功能障碍，具有作为 EH 早期诊断生物标志物的潜力。
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