Fatima Farah, Nawaz Muhammad
Department of Pathology and Forensic Medicine, Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, Ribeirão Preto 14049-900, Brazil.
Noncoding RNA. 2017 Feb 23;3(1):10. doi: 10.3390/ncrna3010010.
Extracellular vesicles (EVs) are nanosized vesicles secreted from virtually all cell types and are thought to transport proteins, lipids and nucleic acids including non-coding RNAs (ncRNAs) between cells. Since, ncRNAs are central to transcriptional regulation during developmental processes; eukaryotes might have evolved novel means of post-transcriptional regulation by trans-locating ncRNAs between cells. EV-mediated transportation of regulatory elements provides a novel source of trans-regulation between cells. In the last decade, studies were mainly focused on microRNAs; however, functions of long ncRNA (lncRNA) have been much less studied. Here, we review the regulatory roles of EV-linked ncRNAs, placing a particular focus on lncRNAs, how they can foster dictated patterns of trans-regulation in recipient cells. This refers to envisaging novel mechanisms of epigenetic regulation, cellular reprogramming and genomic instability elicited in recipient cells, ultimately permitting the generation of cancer initiating cell phenotypes, senescence and resistance to chemotherapies. Conversely, such trans-regulation may introduce RNA interference in recipient cancer cells causing the suppression of oncogenes and anti-apoptotic proteins; thus favoring tumor inhibition. Collectively, understanding these mechanisms could be of great value to EV-based RNA therapeutics achieved through gene manipulation within cancer cells, whereas the ncRNA content of EVs from cancer patients could serve as non-invasive source of diagnostic biomarkers and prognostic indicators in response to therapies.
细胞外囊泡（EVs）是几乎所有细胞类型分泌的纳米级囊泡，被认为在细胞间运输蛋白质、脂质和包括非编码RNA（ncRNAs）在内的核酸。由于ncRNAs在发育过程中对转录调控至关重要；真核生物可能已经进化出通过在细胞间转运ncRNAs进行转录后调控的新方法。EV介导的调控元件运输为细胞间的反式调控提供了新来源。在过去十年中，研究主要集中在微小RNA上；然而，长链非编码RNA（lncRNA）的功能研究较少。在这里，我们综述了与EV相关的ncRNAs的调控作用，特别关注lncRNAs，以及它们如何在受体细胞中促进特定的反式调控模式。这涉及设想受体细胞中引发的表观遗传调控、细胞重编程和基因组不稳定的新机制，最终导致癌症起始细胞表型、衰老和对化疗的抗性的产生。相反，这种反式调控可能在受体癌细胞中引入RNA干扰，导致癌基因和抗凋亡蛋白的抑制；从而有利于肿瘤抑制。总的来说，了解这些机制对于通过癌细胞内基因操作实现基于EV的RNA治疗可能具有重要价值，而癌症患者EVs的ncRNA含量可作为治疗反应中诊断生物标志物和预后指标的非侵入性来源。
