Iparraguirre Leire, Alberro Ainhoa, Hansen Thomas B, Castillo-Triviño Tamara, Muñoz-Culla Maider, Otaegui David
Multiple Sclerosis Unit, Biodonostia Health Research Institute, 20014 San Sebastián, Spain.
Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal.
Biomedicines. 2021 Dec 7;9(12):1850. doi: 10.3390/biomedicines9121850.
(1) Background: Extracellular vesicles (EVs) are released by most cell types and are implicated in several biological and pathological processes, including multiple sclerosis (MS). Differences in the number and cargo of plasma-derived EVs have been described in MS. In this work, we have characterised the EV RNA cargo of MS patients, with particular attention to circular RNAs (circRNAs), which have attracted increasing attention for their roles in physiology and disease and their biomarker potential. (2) Methods: Plasma-derived EVs were isolated by differential centrifugation (20 patients, 8 controls), and RNA-Sequencing was used to identify differentially expressed linear and circRNAs. (3) Results: We found differences in the RNA type distribution, circRNAs being enriched in EVs vs. leucocytes. We found a number of (corrected -value < 0.05) circRNA significantly DE between the groups. Nevertheless, highly structured circRNAs are preferentially retained in leukocytes. Differential expression analysis reports significant differences in circRNA and linear RNA expression between MS patients and controls, as well as between different MS types. (4) Conclusions: Plasma derived EV RNA cargo is not a representation of leukocytes' cytoplasm but a message worth studying. Moreover, our results reveal the interest of circRNAs as part of this message, highlighting the importance of further understanding RNA regulation in MS.
(1) 背景：细胞外囊泡（EVs）由大多数细胞类型释放，并参与多种生物学和病理过程，包括多发性硬化症（MS）。已有研究描述了MS患者血浆来源的EVs在数量和货物方面的差异。在本研究中，我们对MS患者的EV RNA货物进行了表征，特别关注环状RNA（circRNAs），其在生理和疾病中的作用以及作为生物标志物的潜力日益受到关注。(2) 方法：通过差速离心法分离血浆来源的EVs（20例患者，8例对照），并使用RNA测序来鉴定差异表达的线性和环状RNA。(3) 结果：我们发现了RNA类型分布的差异，环状RNA在EVs中比在白细胞中更丰富。我们发现了一些（校正P值<0.05）在两组之间显著差异表达的环状RNA。然而，高度结构化的环状RNA优先保留在白细胞中。差异表达分析报告了MS患者与对照之间以及不同MS类型之间环状RNA和线性RNA表达的显著差异。(4) 结论：血浆来源的EV RNA货物并非白细胞细胞质的代表，但却是一个值得研究的信息。此外，我们的结果揭示了环状RNA作为该信息一部分的重要性，突出了进一步了解MS中RNA调控的重要性。
