Unlike linear RNAs, circular RNAs (circRNAs) form a covalently closed loop that resists degradation, making them remarkably stable in blood, saliva, urine, and other body fluids. This unique property, together with their cancer‑specific expression patterns, has positioned circRNAs as promising candidates for next‑generation liquid biopsy. A new review published in Chinese Medical Journal provides a comprehensive overview of how circulating circRNAs can be used for early cancer detection, prognosis assessment, and therapy monitoring, while also highlighting their emerging role as direct therapeutic targets.
“ CircRNAs are not only stable and abundant in circulation, but they also exhibit high cell‑type and tissue specificity ,” explains Dr. Xingguo Song, corresponding author from Shandong Cancer Hospital and Institute (China). “ Their expression levels change with tumor stage and correlate with key clinical features such as metastasis and drug resistance. This makes them ideal translational tools for non‑invasive cancer management.”
The review details multiple mechanisms by which circRNAs influence cancer biology. Best known as microRNA sponges, circRNAs can also bind to proteins, regulate alternative splicing, modulate epigenetic marks, and even encode short peptides. These diverse functions allow circRNAs to act as either oncogenes or tumor suppressors, affecting nearly every hallmark of cancer—from sustained proliferation and metabolic reprogramming to immune evasion and therapy resistance.
Because of their stability and detectability in peripheral blood, circRNAs are particularly attractive for early diagnosis. The authors discuss how diagnostic panels based on multiple circRNAs can achieve high accuracy, even in early‑stage disease. Beyond diagnosis, specific circRNAs have been linked to poor prognosis across several cancer types. Importantly, circRNAs are not limited to blood; they can be detected in platelets, cerebrospinal fluid, gastric juice, saliva, and urine, greatly expanding the scope of liquid biopsy. Changes in circulating circRNA levels can also reflect treatment response and emerging resistance, positioning them as functional drivers of therapy resistance and actionable therapeutic targets.
The authors also address current challenges, including the need for standardized operating procedures, large prospective validation cohorts, and improved detection methods. Advanced technologies such as nanopore sequencing, droplet digital PCR, and CRISPR‑based assays are expected to overcome these hurdles. Looking ahead, the review envisions a “circRNA‑centric oncology” where endogenous circRNAs enable real‑time monitoring of tumor evolution and synthetic circRNAs serve as programmable therapeutics.
“ The strategic value of circulating circRNAs lies in their dual role as both biomarkers and therapeutic targets ,” concludes Dr. Song. “ They provide real‑time insights into tumor biology while offering opportunities to disrupt oncogenic pathways and reverse therapy resistance. With continued research, we are moving toward a circRNA‑centric era in cancer care .”
Reference
DOI: http://doi.org/10.1097/CM9.0000000000004120
About Associate Professor Xingguo Song from Shandong First Medical University
Dr. Xingguo Song is an Associate Professor in the Department of Clinical Laboratory at Shandong Cancer Hospital and Institute, Shandong First Medical University. He has authored over 20 papers and an H‑index of 22. His research focuses on non‑invasive liquid biopsy biomarkers for cancer, particularly circulating exosomes and circular RNAs (circRNAs). Dr. Song is dedicated to identifying novel diagnostic and prognostic targets for gastrointestinal and thoracic cancers, contributing to the advancement of precision oncology and molecular diagnostics.
Chinese Medical Journal
Literature review
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Circulating circRNAs at the frontier of cancer detection, prognosis, and therapy
24-Jun-2026
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