Wang Yan, Zhang Liang, Yang Rui, Shan Li-Ya, Wang Lu, Zhang Ying-Ying, Li Xin-Zhi, Ma Ke-Tao
Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Ministry of Education, Shihezi University School of Medicine, Shihezi 832000, China.
NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, Shihezi University School of Medicine, Shihezi 832000, China.
Sheng Li Xue Bao. 2022 Oct 25;74(5):751-762.
This study aimed to investigate the differential expression profiles of microRNAs (miRNAs) in peripheral blood lymphocytes between patients with essential hypertension and healthy individuals in Xinjiang Kazakh and to provide insight into the mechanism involved in the pathogenesis of hypertension in this ethnic group. From April 2016 to May 2019, 30 Kazakh patients with essential hypertension in the inpatient and outpatient departments of Cardiology, First Affiliated Hospital of Shihezi University were used as the hypertension group; 30 healthy Kazakh patients were used as the control group. The miRNA expression profiles in peripheral blood lymphocytes of 6 Kazakh hypertensive patients and 6 matched healthy individuals were compared, and the differentially expressed miRNAs were analyzed by cluster analysis, GSEA enrichment analysis, target gene prediction, target gene annotation and other bioinformatics analyses. In addition, qRT-PCR was used to verify the differentially expressed miRNAs. The results showed that compared with the control group, 73 differentially expressed miRNAs were identified in the hypertension group, of which 39 miRNAs were up-regulated and 34 miRNAs were down-regulated. A total of 11 miRNAs related to hypertension were screened by GSEA enrichment analysis, including hsa-miR-100-5p, hsa-miR-150-5p, hsa-miR-299-5p, hsa-miR-299-3p, hsa-miR-296-5p, hsa-miR-196b-5p, hsa-miR-503-5p, hsa-miR-628-5p, hsa-miR-874-3p, hsa-miR-543 and hsa-miR-940. qRT-PCR test found that the expression of hsa-miR-100-5p, hsa-miR-299-5p, hsa-miR-299-3p, hsa-miR-196b-5p, hsa-miR-503-5p, hsa-miR-628-5p and hsa-miR-543 was up-regulated, while the expression of hsa-miR-150-5p, hsa-miR-296-5p, hsa-miR-874-3p and hsa-miR-940 was down-regulated in the hypertension group compared with the control group. The expression trend in the gene chip was consistent with the results verified by qRT-PCR. Using online database to predict target genes of 11 miRNAs related to hypertension, we found that a total of 1 647 target genes might be regulated by these 11 miRNAs. GO function enrichment showed that (a) in biological processes, the predicted hypertension related target genes are mainly relevant to nervous system development, cellular localization, regulation of cellular metabolic process, generation of neurons and positive regulation of biological process; (b) In terms of cellular components, they are mainly related to membrane-bounded organelle, cytoplasm, intracellular membrane-bounded organelle, synapse part, neuron part, and nucleoplasm; (c) In terms of molecular function, they are mainly related to protein binding, transcription regulatory region DNA binding, RNA polymerase II regulatory region DNA binding, transcription regulator activity, and ion binding. KEGG enrichment analysis showed that the p53 signaling pathway, adrenergic signaling in cardiomyocytes, cAMP signaling pathway, TGF-β signaling pathway, endocrine and other factor-regulated calcium reabsorption, mTOR signaling pathway, and aldosterone-regulated sodium reabsorption may be related to the occurrence and development of hypertension. In conclusion, there are significant differences in the expression of miRNAs in peripheral blood lymphocytes between Kazakh patients with essential hypertension and healthy people. The differentially expressed miRNAs may be related to the occurrence and development of essential hypertension in Kazakh. However, the underlying mechanism needs to be further explored and verified.
本研究旨在探讨新疆哈萨克族原发性高血压患者与健康个体外周血淋巴细胞中微小RNA(miRNA)的差异表达谱,为该民族高血压发病机制的研究提供线索。2016年4月至2019年5月,选取石河子大学第一附属医院心内科住院及门诊的30例哈萨克族原发性高血压患者作为高血压组;30例健康哈萨克族患者作为对照组。比较6例哈萨克族高血压患者和6例匹配的健康个体外周血淋巴细胞中的miRNA表达谱,并通过聚类分析、基因集富集分析(GSEA)、靶基因预测、靶基因注释等生物信息学分析方法对差异表达的miRNA进行分析。此外,采用qRT-PCR验证差异表达的miRNA。结果显示,与对照组相比,高血压组共鉴定出73个差异表达的miRNA,其中39个miRNA上调,34个miRNA下调。通过GSEA富集分析筛选出11个与高血压相关的miRNA,包括hsa-miR-100-5p、hsa-miR-150-5p、hsa-miR-299-5p、hsa-miR-299-3p、hsa-miR-296-5p、hsa-miR-196b-5p、hsa-miR-503-5p、hsa-miR-628-5p、hsa-miR-874-3p、hsa-miR-543和hsa-miR-940。qRT-PCR检测发现,与对照组相比,高血压组中hsa-miR-100-5p、hsa-miR-299-5p、hsa-miR-299-3p、hsa-miR-196b-5p、hsa-miR-503-5p、hsa-miR-628-5p和hsa-miR-543表达上调,而hsa-miR-150-5p、hsa-miR-296-5p、hsa-miR-874-3p和hsa-miR-940表达下调。基因芯片中的表达趋势与qRT-PCR验证结果一致。利用在线数据库预测11个与高血压相关的miRNA的靶基因,发现共有1647个靶基因可能受这11个miRNA调控。GO功能富集显示:(a)在生物学过程中,预测的高血压相关靶基因主要与神经系统发育、细胞定位、细胞代谢过程调控、神经元生成及生物过程的正调控相关;(b)在细胞成分方面,主要与膜结合细胞器、细胞质、细胞内膜结合细胞器、突触部分、神经元部分及核质相关;(c)在分子功能方面,主要与蛋白质结合、转录调控区DNA结合、RNA聚合酶II调控区DNA结合、转录调节因子活性及离子结合相关。KEGG富集分析显示,p53信号通路、心肌细胞肾上腺素能信号通路、cAMP信号通路、TGF-β信号通路、内分泌及其他因子调节的钙重吸收、mTOR信号通路和醛固酮调节的钠重吸收可能与高血压的发生发展有关。综上所述,哈萨克族原发性高血压患者与健康人外周血淋巴细胞中miRNA表达存在显著差异。差异表达的miRNA可能与哈萨克族原发性高血压的发生发展有关。然而,其潜在机制仍需进一步探索和验证。