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基于高通量测序的绝经后骨质疏松症女性血清外泌体 microRNA 表达谱鉴定。

Identification of Serum Exosomal MicroRNA Expression Profiling in Menopausal Females with Osteoporosis by High-throughput Sequencing.

机构信息

Department of Orthopedics and Traumatology, First Affiliated Hospital, Jinan University, Guangzhou, 510632, China.

Department of Orthopedics, Central People's Hospital of Zhanjiang, Zhanjiang, 524045, China.

出版信息

Curr Med Sci. 2020 Dec;40(6):1161-1169. doi: 10.1007/s11596-020-2306-x. Epub 2021 Jan 11.

Abstract

Estrogen deficiency, which mainly occurs in postmenopausal women, is a primary reason for osteoporosis in clinical diagnosis. However, the molecular regulation of osteoporosis in menopausal females is still not adequately explained in the literature, with the diagnosis and treatment for osteoporosis being limited. Herein, exosomal microRNAs (miRNAs) were used to evaluate their diagnosis and prediction effects in menopausal females with osteoporosis. In this study, 6 menopausal females without osteoporosis and 12 menopausal females with osteoporosis were enrolled. The serum exosomes were isolated, and the miRNA expression was detected by miRNA high-throughput sequencing. Exosomal miRNA effects were analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. The miRNA-targeted genes were evaluated by Targetscan 7.2 and the protein-protein interactions (PPI) by STRING. Hub genes were analyzed by the CytoHubba app of Cytoscape. The results showed that 191 aberrant miRNAs were found in the group of menopausal females with osteoporosis, including 72 upregulated miRNAs and 121 downregulated miRNAs. Aberrant miRNAs were involved in many signaling pathways, such as the Wnt, MAPK, and Hippo pathways. Based on PPI network analysis, FBXL3, FBXL13, COPS2, UBE2D3, DCUN1D1, DCUN1D4, CUL3, FBXO22, ASB6, and COMMD2 were the 10 most notable genes in the PPI network. In conclusion, aberrant serum exosomal miRNAs were associated with an altered risk of osteoporosis in menopausal females and may act as potential biomarkers for the prediction of risk of osteoporosis in menopausal females.

摘要

雌激素缺乏主要发生在绝经后妇女中,是临床诊断骨质疏松症的主要原因。然而,文献中仍未充分解释绝经后女性骨质疏松症的分子调控,骨质疏松症的诊断和治疗受到限制。在此,使用外泌体 microRNAs(miRNAs)来评估其在绝经后骨质疏松症女性中的诊断和预测效果。本研究纳入了 6 名无骨质疏松症的绝经后女性和 12 名有骨质疏松症的绝经后女性。分离血清外泌体,通过 miRNA 高通量测序检测 miRNA 表达。通过基因本体论和京都基因与基因组百科全书分析分析外泌体 miRNA 的作用。通过 Targetscan 7.2 评估 miRNA 靶向基因,通过 STRING 评估蛋白质-蛋白质相互作用(PPI)。通过 Cytoscape 的 CytoHubba 应用程序分析枢纽基因。结果显示,骨质疏松症绝经后女性组中发现了 191 个异常 miRNA,包括 72 个上调 miRNA 和 121 个下调 miRNA。异常 miRNA 参与了许多信号通路,如 Wnt、MAPK 和 Hippo 通路。基于 PPI 网络分析,FBXL3、FBXL13、COPS2、UBE2D3、DCUN1D1、DCUN1D4、CUL3、FBXO22、ASB6 和 COMMD2 是 PPI 网络中 10 个最显著的基因。总之,异常血清外泌体 miRNAs 与绝经后女性骨质疏松症风险增加有关,可能作为绝经后女性骨质疏松症风险预测的潜在生物标志物。

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