Department of Life and Health Sciences, School of Sciences and Engineering, University of Nicosia, Nicosia, Cyprus.
IUBMB Life. 2021 Dec;73(12):1400-1405. doi: 10.1002/iub.2575. Epub 2021 Nov 14.
Exosomes are 30-100 nm endosome-derived membrane vesicles, that contain specific RNA transcripts including mRNAs, and microRNAs (miRNAs) and have been implicated in cell-to-cell communication. Exosomal miRNAs in blood circulation have been attracting major interest as potential diagnostic and prognostic biomarkers in a variety of diseases including stroke, cancer, and inflammatory disorders. Despite the progress made in the utilization of circulating exosomal miRNAs as biomarkers for various human diseases and conditions, there are still difficulties in functionally utilizing such methods in the clinic due to the high variability observed among subjects. Attempts to use miRNA signatures have improved but have not eliminated the problem. Additionally, standardized laboratory practices may partially reduce variability but there is still an unknown biological factor that hinders the proper use of miRNAs as biomarkers. We hypothesize that this variability might be partially attributed to a differential interaction among circulating exosomes carrying those miRNAs with endothelial surface molecules that themselves may vary among individuals due to secondary conditions, for example, inflammation status. This differential interaction could potentially add variability to the level of the examined miRNA that is not directly attributed to the primary condition under study.
外泌体是 30-100nm 大小的内体衍生膜囊泡,其中包含特定的 RNA 转录本,包括 mRNAs 和 microRNAs(miRNAs),并被认为参与细胞间通讯。血液循环中的外泌体 miRNAs 作为各种疾病(包括中风、癌症和炎症性疾病)的潜在诊断和预后生物标志物引起了极大的关注。尽管在将循环外泌体 miRNAs 作为各种人类疾病和病症的生物标志物方面取得了进展,但由于在研究对象中观察到的高度变异性,在临床上功能上利用这些方法仍然存在困难。尝试使用 miRNA 特征已得到改善,但并未消除该问题。此外,标准化的实验室实践可能会部分降低变异性,但仍存在未知的生物学因素阻碍 miRNA 作为生物标志物的正确使用。我们假设这种变异性可能部分归因于携带这些 miRNAs 的循环外泌体与内皮表面分子之间的差异相互作用,而这些分子本身可能由于二次条件(例如炎症状态)而在个体之间发生变化。这种差异相互作用可能会增加所检查的 miRNA 的水平的变异性,而这种变异性并不是直接归因于正在研究的主要病症。