Exosomal circRNAs: new players in the field of cholangiocarcinoma

Abstract

Cholangiocarcinoma (CCA) is a deadly cancer worldwide associated with limited therapeutic options. A recent study published in Clinical Science by Wang and colleagues [Clin. Sci. (2019) 133(18), 1935–1953] brought new perspectives to CCA management and therapy by focusing on circular RNAs (circRNAs). CircRNAs belong to an emerging class of functional non-coding RNAs (ncRNAs) regulating numerous biological processes. Notably, circRNAs have been associated with cancer onset and progression, although reports in CCA are very limited so far. In this work, the expression of circular RNA circ-0000284 (aka circHIPK3) was specifically elevated in CCA cell lines, human tumor tissues and plasma exosomes. Gain and loss of function approaches were performed to better understand the molecular mechanisms regulated by circ-0000284. Notably, the authors evaluated the role of circ-0000284 as a microRNA (miRNA) sponge. By prediction analysis and functional tests, a direct interaction was demonstrated with miR-637 that targets lymphocyte antigen-6 E (LY6E). Increased expression of circ-0000284 was associated with enhanced migration, invasion and proliferation of CCA cell lines. Interestingly, exosomal-mediated circ-0000284 was reported to exhibit pro-oncogenic effects on surrounding normal cells. Altogether, these data highlight circRNAs not only as new players in CCA pathogenesis but also as promising molecules for innovative non-invasive biomarkers, as circRNAs are enriched and stable in exosomes. Further investigations on extracellular vesicles should provide the necessary tools to improve CCA diagnosis, and move toward targeted-therapies.

Circular RNAs in body fluids as cancer biomarkers: the new frontier of liquid biopsies

“…In patients with nasopharyngeal carcinoma, serum levels of circRNA_0000285 were increased and significantly correlated with the differentiation grade, tumour size, lymph node metastasis, distal metastasis, and TNM stage, indicating an independent prognostic indicator for nasopharyngeal carcinoma [89]. In addition, hsa_circ_ 0109046 and hsa_circ_0002577 were upregulated in the serum of patients with endometrial cancer [90], and exosomal circ-0000284 was overexpressed in patients with cholangiocarcinoma [91].…”

Small Extracellular Vesicles: A Novel Avenue for Cancer Management

“…ncRNAs from sEVs are also promising clinical biomarkers. In cholangiocarcinoma, several lncRNAs ( 139 ) and circular RNAs ( 140 , 141 ) from circulating sEVs have been correlated with metastasis and have been proposed as cancer biomarkers ( 142 ). An ongoing clinical trial is investigating the ability of a group of serum lncRNAs to detect early-stage lung tumors to improve clinical outcomes ( 143 ).…”

Noncoding RNAs in subchondral bone osteoclast function and their therapeutic potential for osteoarthritis

“…Alternative functions include transcriptional regulators, combining binding with RNA-binding proteins, and even translation to produce polypeptides [52,53]. circRNAs can also be secreted into the intercellular space and transported into adjacent cells or body fluids to regulate cell activities [54,55]. Compared to investigations into the roles of miRNAs in osteoclastogenesis, studies focusing on circRNAs have been limited.…”