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Going circular: history, present, and future of circRNAs in cancer

Journal

ONCOGENE
Volume 42, Issue 38, Pages 2783-2800

Publisher

SPRINGERNATURE
DOI: 10.1038/s41388-023-02780-w

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To date, thousands of circRNAs, which are highly abundant and conserved single-stranded RNA molecules shaped into ring structures, have been identified. CircRNAs have been shown to regulate gene expression and exhibit tissue- and development-specific expression patterns associated with normal and disease conditions, including cancer. They have drawn attention as potential diagnostic and prognostic biomarkers in cancer due to their stability and resistance to ribonucleases. However, their circular shape limits their annotation and a complete understanding of their functions is still lacking, making their detection and biomedical application challenging.
To date, thousands of highly abundant and conserved single-stranded RNA molecules shaped into ring structures (circRNAs) have been identified. CircRNAs are multifunctional molecules that have been shown to regulate gene expression transcriptionally and post-transcriptionally and exhibit distinct tissue- and development-specific expression patterns associated with a variety of normal and disease conditions, including cancer pathogenesis. Over the past years, due to their intrinsic stability and resistance to ribonucleases, particular attention has been drawn to their use as reliable diagnostic and prognostic biomarkers in cancer diagnosis, treatment, and prevention. However, there are some critical caveats to their utility in the clinic. Their circular shape limits their annotation and a complete functional elucidation is lacking. This makes their detection and biomedical application still challenging. Herein, we review the current knowledge of circRNA biogenesis and function, and of their involvement in tumorigenesis and potential utility in cancer-targeted therapy.

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