Extracellular RNAs as potential biomarkers for cancer

Abstract

The discovery that all cells secrete extracellular vesicles (EVs) to shuttle proteins and nucleic acids to recipient cells suggested they play an important role in intercellular communication. EVs are widely distributed in many body fluids, including blood, cerebrospinal fluid, urine and saliva. Exosomes are nano-sized EVs of endosomal origin that regulate many pathophysiological processes including immune responses, inflammation, tumour growth, and infection. Healthy individuals release exosomes with a cargo of different RNA, DNA, and protein contents into the circulation, which can be measured non-invasively as biomarkers of healthy and diseased states. Cancer-derived exosomes carry a unique set of DNA, RNA, protein and lipid reflecting the stage of tumour progression, and may serve as diagnostic and prognostic biomarkers for various cancers. However, many gaps in knowledge and technical challenges in EVs and extracellular RNA (exRNA) biology, such as mechanisms of EV biogenesis and uptake, exRNA cargo selection, and exRNA detection remain. The NIH Common Fund-supported exRNA Communication Consortium was launched in 2013 to address major scientific challenges in this field. This review focuses on scientific highlights in biomarker discovery of exosome-based exRNA in cancer and its possible clinical application as cancer biomarkers.

Potential Role of Exosomes in Ischemic Stroke Treatment

“…In addition, proteins (such as brain-derived neurotrophic factor, Zeb2/Axin2) of exosomes participate in brain repair, involving neurogenesis, antiapoptotic processes, and synaptic transmission [ 40 , 41 ]. Of the exosome cargo, microRNAs appear to participate in multiple biological processes [ 42 ]. For instance, miRNA-143 is involved in angiogenesis [ 43 ], while miR-17-92 cluster and miR-26a are related to neurogenesis and axonal growth signals [ 44 , 45 ].…”

Clinical and Molecular Biomarkers for Diagnosis and Staging of NAFLD

“…A key feature making cf-RNAs excellent biomarkers is their high stability: these molecules are protected by endogenous RNases and are resistant to different external insults, such as multiple thaw–draw cycles, boiling, extreme PH conditions, prolonged storage and exogenous RNase treatment [ 79 , 80 ]. Circulating RNAs are extremely stable because they are not present in a free form in the circulation; instead, they are encapsulated in membranous vesicles (micro-vesicles, exosomes, apoptotic bodies), or alternatively complexed to RNA binding proteins (i.e., NPM1, Argonauta 2) or associated with lipoproteins.…”

tRNA Metabolism and Lung Cancer: Beyond Translation

“…Various RNA species are released into the extracellular space in the form of extracellular vesicles (EVs) or complexes with proteins, collectively known as extracellular RNA (exRNA) ( Happel et al, 2020 ). Interestingly, exRNAs could not only serve as potential biomarkers for lung cancer ( Wang et al, 2020 ) but also could act as signaling molecules to regulate tumorigenesis ( Li et al, 2019 ).…”