Circular RNA, A Molecule with Potential Chemistry and Applications in RNA-based Cancer Therapeutics: An Insight into Recent Advances

Non-coding RNAs (ncRNAs) are functional RNA molecules that do not code for proteins. Among these, circular RNAs (circRNAs) represent a recently identified class of endogenous ncRNAs with a pivotal role in gene regulation, alongside short ncRNAs (e.g., microRNAs or miRNAs) and long non-coding RNAs (lncRNAs). CircRNAs are characterized by their single-stranded, covalently closed circular structure, which lacks polyadenylated tails and 5'-3' ends. This unique circular conformation makes them resistant to exonuclease degradation, rendering them more stable than linear RNAs, such as mRNAs in human blood cells, which highlights their potential as biomarkers. Both linear and circular RNAs are derived from pre-mRNA precursors. However, while linear RNAs are produced through conventional splicing, circRNAs are primarily formed through a process known as reverse splicing. CircRNAs can be categorized into five basic types: exon circRNAs, circular intronic RNAs, exon–intron circRNAs, intergenic circRNAs, and fusion circRNAs. These molecules have been shown to significantly influence key hallmarks of cancer, including sustained growth signaling, proliferation, angiogenesis, resistance to apoptosis, unlimited replicative potential, and metastasis. This article will delve into the biogenesis and functions of circRNAs, explore their roles in cancer, and discuss their potential applications as therapeutic options and diagnostic biomarkers.

Graphical Abstract