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计算鉴定和表征血库保存的人类血小板中的新 microRNAs。

Computational Identification and Characterization of New microRNAs in Human Platelets Stored in a Blood Bank.

机构信息

Laboratory of Human Cytogenetics, Institute of Biological Sciences, Federal University of Pará, Belém, PA 66075-110, Brazil.

Laboratory of Molecular Biology, Ophir Loyola Hospital, Belém, PA 66063-240, Brazil.

出版信息

Biomolecules. 2020 Aug 12;10(8):1173. doi: 10.3390/biom10081173.

Abstract

Platelet concentrate (PC) transfusions are widely used to save the lives of patients who experience acute blood loss. MicroRNAs (miRNAs) comprise a class of molecules with a biological role which is relevant to the understanding of storage lesions in blood banks. We used a new approach to identify miRNAs in normal human platelet sRNA-Seq data from the GSE61856 repository. We identified a comprehensive miRNA expression profile, where we detected 20 of these transcripts potentially expressed in PCs stored for seven days, which had their expression levels analyzed with simulations of computational biology. Our results identified a new collection of miRNAs (miR-486-5p, miR-92a-3p, miR-103a-3p, miR-151a-3p, miR-181a-5p, and miR-221-3p) that showed a sensitivity expression pattern due to biological platelet changes during storage, confirmed by additional quantitative real-time polymerase chain reaction (qPCR) validation on 100 PC units from 500 healthy donors. We also identified that these miRNAs could transfer regulatory information on platelets, such as members of the let-7 family, by regulating the gene, which is a deubiquitinating enzyme highly expressed in platelet hyperactivity. Our results also showed that the target genes of these miRNAs play important roles in signaling pathways, cell cycle, stress response, platelet activation and cancer. In summary, the miRNAs described in this study, have a promising application in transfusion medicine as potential biomarkers to also measure the quality and viability of the PC during storage in blood banks.

摘要

血小板浓缩物 (PC) 输注被广泛用于挽救经历急性失血的患者的生命。微小 RNA(miRNA)是一类具有生物学功能的分子,与理解血库中储存损伤有关。我们使用一种新方法从 GSE61856 存储库中鉴定正常人类血小板 sRNA-Seq 数据中的 miRNA。我们确定了一个全面的 miRNA 表达谱,其中我们检测到 20 种这些转录物可能在储存七天的 PCs 中表达,并对其表达水平进行了模拟计算生物学分析。我们的结果确定了一组新的 miRNA(miR-486-5p、miR-92a-3p、miR-103a-3p、miR-151a-3p、miR-181a-5p 和 miR-221-3p),它们表现出敏感性表达模式,这是由于储存过程中血小板的生物学变化,通过对 500 名健康供体的 100 个 PC 单位进行额外的定量实时聚合酶链反应 (qPCR) 验证得到了证实。我们还发现这些 miRNA 可以通过调节基因(一种高度表达于血小板活性亢进的去泛素化酶)在血小板上传递调节信息,例如 let-7 家族成员。我们的结果还表明,这些 miRNA 的靶基因在信号通路、细胞周期、应激反应、血小板激活和癌症中发挥重要作用。总之,本研究中描述的 miRNA 作为潜在的生物标志物,在输血医学中有很好的应用前景,可用于测量血库中 PC 在储存期间的质量和活力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d146/7464399/b4d346575e3e/biomolecules-10-01173-g001.jpg

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