The Malignant Role of Exosomes as Nanocarriers of Rare RNA Species

Abstract

Nowadays, advancements in the oncology sector regarding diagnosis methods allow us to specifically detect an increased number of cancer patients, some of them in incipient stages. However, one of the main issues consists of the invasive character of most of the diagnosis protocols or complex medical procedures associated with it, that impedes part of the patients to undergo routine checkups. Therefore, in order to increase the number of cancer cases diagnosed in incipient stages, other minimally invasive alternatives must be considered. The current review paper presents the value of rare RNA species isolated from circulatory exosomes as biomarkers of diagnosis, prognosis or even therapeutic intervention. Rare RNAs are most of the time overlooked in current research in favor of the more abundant RNA species like microRNAs. However, their high degree of stability, low variability and, for most of them, conservation across species could shift the interest toward these types of RNAs. Moreover, due to their low abundance, the variation interval in terms of the number of sequences with differential expression between samples from healthy individuals and cancer patients is significantly diminished and probably easier to interpret in a clinical context.

Long non‐coding RNA and transfer RNA‐derived small fragments in exosomes are potential biomarkers for canine oral melanoma

“…Two scaRNAs (SCARNA2 and SCARNA22) have been found to play an oncogenic role in colorectal cancer and multiple myeloma 22–24 . SNORD20 is reported as one of the most highly expressed RNAs in glioblastoma cell lines 8 . In another study, melanoma exosomes were found to be enriched with SNORD83A and SNORD89 25 .…”

“…In general, novel sRNAs possess high stability and low variability, and are conserved across a range of species. Accordingly, they can be regarded as a more reliable source of non‐invasive biomarkers for the investigation of cancer than commonly used miRNAs or lncRNAs 8 …”

“…Melanomas are highly aggressive skin cancers in canine as well as human medicine. They can progress to a metastatic phase dramatically, with a concomitantly poor prognosis 8,11–13 . Canine oral melanoma is the most common oral tumour in dogs, accounting for 7% of all malignant tumours in dogs, 13 and has been proposed as a spontaneous model for human melanoma 12 .…”

Exosomal RNAs in diagnosis and therapies

“…According to ExoCarta, an internet exosome database ( http://www.exocarta.org/ ), 286 studies identified 2838 miRNAs and 3408 mRNAs, respectively (June 2021). In addition to miRNAs and mRNAs, exosomes have also been documented to contain rRNAs, tRNAs, small Cajal body-specific RNAs (scaRNAs), small nucleolar RNAs (snoRNAs), small nuclear RNAs (snRNAs), and piwi-interacting RNA (piRNA) from a previous investigation that assessed the exosomal content of exosomes derived from serum, plasma, urine, and Cerebrospinal Fluid [ 16 ]. Recently, exoRBase, a database developed by Fudan University Shanghai Cancer Center collected and characterized RNA species in human blood exosomes, and through RNA-sequencing data analyses and experimental findings from other literature, they detected 58,330 cirRNAs, 15,501 lncRNAs, and 18,333 mRNAs [ 17 ].…”

Interplay within tumor microenvironment orchestrates neoplastic RNA metabolism and transcriptome diversity

“…For a detailed analysis on EV lncRNA-mediated crosstalk between tumor cells and the recipient cells in the TME, please refer to M. Zhang, Shi, et al (2020) andTellez-Gabriel &Heymann (2019). Additional studies have also identified other EVresident RNAs, such as small nucleolar RNAs (snoRNAs), small nuclear RNAs (snRNAs), transfer RNAs (tRNAs), ribosomal RNAs (rRNAs), and piwi-interacting RNAs (piRNAs; Nolte-t' Hoen et al, 2012;Zimta et al, 2020). However, their detailed modes of action in recipient cells remain to be fully elucidated.…”