Lovisa Federica, Di Battista Piero, Gaffo Enrico, Damanti Carlotta C, Garbin Anna, Gallingani Ilaria, Carraro Elisa, Pillon Marta, Biffi Alessandra, Bortoluzzi Stefania, Mussolin Lara
Clinic of Pediatric Onco-Hematology, Department of Women's and Children's Health, University of Padova, Padova, Italy.
Istituto di Ricerca Pediatrica Città della Speranza, Padova, Italy.
Front Oncol. 2020 Feb 27;10:238. doi: 10.3389/fonc.2020.00238. eCollection 2020.
Emerging evidence indicates that extracellular vesicles, particularly exosomes, play a role in several biological processes and actively contribute to cancer development and progression, by carrying and delivering proteins, transcripts and small RNAs (sRNAs). There is high interest in studying exosomes of cancer patients both to develop non-invasive liquid biopsy tests for risk stratification and to elucidate their possible involvement in disease mechanisms. We profiled by RNA-seq the sRNA content of circulating exosomes of 20 pediatric patients with Anaplastic Large Cell Lymphoma (ALCL) and five healthy controls. Our analysis disclosed that non-miRNA derived sRNAs constitute the prominent fraction of sRNA loaded in exosomes and identified 180 sRNAs significantly more abundant in exosomes of ALCL patients compared to controls. YRNA fragments, accounting for most of exosomal content and being significantly increased in ALCL patients, were prioritized for further investigation by qRT-PCR. Quantification of fragments and full-length sequences disclosed that the latter are massively loaded into exosomes of ALCL patients with more advanced and aggressive disease. These results are discussed in light of recent findings on the role of in the modulation of tumor microenvironment.
新出现的证据表明，细胞外囊泡，尤其是外泌体，通过携带和传递蛋白质、转录本和小RNA（sRNA），在多个生物学过程中发挥作用，并积极促进癌症的发展和进展。人们对研究癌症患者的外泌体非常感兴趣，既为了开发用于风险分层的非侵入性液体活检测试，也为了阐明它们可能参与疾病机制。我们通过RNA测序分析了20例间变性大细胞淋巴瘤（ALCL）儿科患者和5名健康对照者循环外泌体的sRNA含量。我们的分析表明，非miRNA衍生的sRNA构成了外泌体中加载的sRNA的主要部分，并鉴定出180种sRNA在ALCL患者的外泌体中比对照组明显更丰富。YRNA片段占外泌体内容物的大部分，并且在ALCL患者中显著增加，因此被优先通过qRT-PCR进行进一步研究。对片段和全长序列的定量分析表明，全长序列大量加载到疾病更晚期和侵袭性更强的ALCL患者的外泌体中。根据最近关于YRNA在调节肿瘤微环境中的作用的发现对这些结果进行了讨论。
