Exosomal circRNAs as novel cancer biomarkers: Challenges and opportunities

Abstract

Identifying high specificity and sensitivity biomarkers has always been the focus of research in the field of non-invasive cancer diagnosis. Exosomes are extracellular vesicles with a lipid bilayer membrane that can be released by all types of cells, which contain a variety of proteins, lipids, and a variety of non-coding RNAs. Increasing research has shown that the lipid bilayer can effectively protect the nucleic acid in exosomes. In cancers, tumor cell-derived exosomal circRNAs can act on target cells or organs through the transport of exosomes, and then participate in the regulation of tumor development and metastasis. Since exosomes exist in various body fluids and circRNAs in exosomes exhibit high stability, exosomal circRNAs have the potential as biomarkers for early and minimally invasive cancer diagnosis and prognosis judgment. In this review, we summarized circRNAs and their biological roles in cancers, with the emerging value biomarkers in cancer diagnosis, disease judgment, and prognosis observation. In addition, we briefly compared the advantages of exosomal circRNAs as biomarkers and the current obstacles in the exosome isolation technology, shed light to the future development of this technology.

Urinary extracellular vesicles: Assessment of pre‐analytical variables and development of a quality control with focus on transcriptomic biomarker research

“…EV cargo is comprised of proteins, several RNA species, DNA, metabolites and lipids (Malkin & Bratman, 2020 ; Raposo & Stoorvogel, 2013 ), which are loaded to EV during their biogenesis (Merchant et al., 2017 ). As EV cargo can capture the physiological or pathophysiological state of their parental cells, EV are a promising source of biomarkers for diseases of diverse aetiology (Dickhout & Koenen, 2018 ; Guha et al., 2019 ; Pang et al., 2020 ; Wang et al., 2021 ). In addition, the bilipid‐layer encapsulated cargo is protected, for example, from proteases and nucleases (Kim et al., 2017 ).…”

The Biological Functions and Clinical Values of Exosomal Circular RNAs in Hepatocellular Carcinoma

“…Some evidence demonstrated that circRNAs had abundant miRNA binding sites and exerted important biological functions by stabilizing microRNAs (miRNAs), regulating alternative splicing and acting as miRNA inhibitors (‘sponges’), protein ‘decoys’, or by encoding small peptides ( 31 , 32 ). Tumor cell-derived exosomal circRNAs can act on target cells or organs by the transport of exosomes and play oncogenic or tumor suppressive roles during tumor development ( 33 ). With the rise of exosome research, some researchers have investigated the relationship between exosomes and circRNAs in tumors and concluded that circRNAs in exosomes can work as novel biomarkers for tumor diagnosis, thus providing a new development direction for tumor diagnosis ( 33 , 34 ).…”

“…Tumor cell-derived exosomal circRNAs can act on target cells or organs by the transport of exosomes and play oncogenic or tumor suppressive roles during tumor development ( 33 ). With the rise of exosome research, some researchers have investigated the relationship between exosomes and circRNAs in tumors and concluded that circRNAs in exosomes can work as novel biomarkers for tumor diagnosis, thus providing a new development direction for tumor diagnosis ( 33 , 34 ). Dou et al.…”

Genomic Landscape of Liquid Biopsy for Hepatocellular Carcinoma Personalized Medicine

“…One more type of ncRNAs is circRNAs that are well-expressed at low but stable levels in different species and exhibit cell-type, tissuetype and developmental-stage specificity and regulatory potency (117). Due to these features, exosomal circRNAs have a biomarker potential for early and minimally invasive cancer diagnosis and prognosis (118,119). Indeed, three isoforms of circPTGR1 are upregulated in serum exosomes from HCC patients and associate with the disease clinical stage and prognosis.…”