Wang Shengyan, Ma Jie, Qiu Huiping, Liu Shizhen, Zhang Shouli, Liu Huihui, Zhang Peili, Ge Ri-Li, Li Guojie, Cui Sen
Department of Clinical Medicine, Qinghai Institute of Health Sciences, Xining, China; Research Center for High Altitude Medicine, Key Laboratory of High Altitude Medicine (Ministry of Education), Key Laboratory of Application and Foundation for High Altitude Medicine Research in Qinghai Province (Qinghai-Utah Joint Research Key Lab for High Altitude Medicine), Qinghai University, Xining, China.
Department of Hematology and Rheumatology, Qinghai Institute of Hematology, Qinghai University Affiliated Hospital, Xining, China.
Blood Cells Mol Dis. 2023 Jan;98:102707. doi: 10.1016/j.bcmd.2022.102707. Epub 2022 Oct 29.
High-altitude polycythemia (HAPC) is a chronic mountain sickness characterized by multiple severe ill-effects. Its pathogenesis is still unclear, and till date, no study has been conducted to investigate the plasma exome profile of Tibetan patients with HAPC. In this study, we aimed to elucidate the pathogenesis of HAPC by determining the microRNA (miRNA) signatures. We compared the plasma exosome miRNA expression profiles of eight patients with HAPC and eight healthy controls using next-generation miRNA sequencing. Further, we extracted and identified plasma exosomes using transmission electron microscopy, nanoparticle tracking analysis, and western blotting. We used quantitative reverse-transcription polymerase chain reaction (qRT-PCR) to validate differentially expressed plasma exosomal miRNAs. Finally, we analyzed the diagnostic values of the differentially expressed miRNAs for HAPC using receiver operating characteristic (ROC) curves. We detected 2007 miRNAs from confirmed plasma exosomes, including 1342 known miRNAs and 665 newly predicted miRNAs. We verified the expression of the top 10 differentially expressed miRNAs via qRT-PCR. Patients with HAPC showed significantly upregulated hsa-miR-122-5p, hsa-miR-423-5p, hsa-miR-4433b-3p, hsa-miR-1291, and hsa-miR-106b-5p expression levels, while hsa-miR-200c-3p expression was downregulated. This study may provide background knowledge for future studies on HAPC studies, which may further facilitate the development of novel therapies against this common disease.
高原红细胞增多症（HAPC）是一种以多种严重不良影响为特征的慢性高山病。其发病机制尚不清楚，迄今为止，尚未有研究对HAPC藏族患者的血浆外显子组特征进行调查。在本研究中，我们旨在通过确定微小RNA（miRNA）特征来阐明HAPC的发病机制。我们使用下一代miRNA测序比较了8例HAPC患者和8例健康对照者的血浆外泌体miRNA表达谱。此外，我们使用透射电子显微镜、纳米颗粒跟踪分析和蛋白质印迹法提取并鉴定了血浆外泌体。我们使用定量逆转录聚合酶链反应（qRT-PCR）来验证差异表达的血浆外泌体miRNA。最后，我们使用受试者工作特征（ROC）曲线分析了差异表达的miRNA对HAPC的诊断价值。我们从已确认的血浆外泌体中检测到2007种miRNA，包括1342种已知miRNA和665种新预测的miRNA。我们通过qRT-PCR验证了前10种差异表达miRNA的表达。HAPC患者的hsa-miR-122-5p、hsa-miR-423-5p、hsa-miR-4433b-3p、hsa-miR-1291和hsa-miR-106b-5p表达水平显著上调，而hsa-miR-200c-3p表达下调。本研究可能为未来HAPC研究提供背景知识，这可能进一步促进针对这种常见疾病的新疗法的开发。
