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Circular RNA (circRNA) as emerging biomarkers

Circular RNAs (circRNAs) are emerging as promising biomarkers due to their stability, tissue specificity, and involvement in various biological processes. The unique characteristics and biological functions of circRNAs make them promising biomarkers for the diagnosis and prognosis of multiple diseases, as well as a therapeutic target.

circRNAs are closed RNAs found in a wide range of biological systems with essential characteristics and multiple biological functions. circRNAs are ubiquitously distributed in eukaryotic cells, exhibiting tissue-specific expression and being constant, abundant, and highly conserved, making them ideal markers for diagnosis and prognosis.

CircRNAs expressed in the hematopoietic compartment act as modulators of the pathological features of hematological cells. In particular, several circular RNAs (circRNAs) are known to enhance or inhibit tumor progression in blood malignancies, such as multiple myeloma. Cancer tissues atypically express circRNAs, and their alteration is implicated in the occurrence and progression of tumors as they control cancer dynamics in different malignancies. Circular RNAs function through base-pairing, binding proteins, and self-translation.

In the human genome, only about 2% of the genes code for proteins. The remainder of the genome consists of non-coding RNAs (ncRNAs). ncRNAs can control cellular functions including growth, differentiation, and programmed cell death. ncRNAs can be classified into short and long ncRNAs, corresponding to their extent, and circular RNAs (circRNAs).

circRNAs represent a novel class of biomarkers with the potential to enhance disease diagnosis, prognosis, and treatment strategies. Medical researchers now increasingly investigate circRNAs for their potential in cancer diagnosis, prognosis, and even as therapeutic targets. However, further research and clinical validation are necessary to harness their potential fully.

CircRNAs have a closed-loop structure, making them resistant to exonuclease degradation, unlike linear RNAs, which contributes to their high stability and longer half-lives. CircRNAs exhibit tissue-specific and stage-specific expression patterns, indicating the specific tissue or developmental stage where a disease process is occurring.

CircRNAs are found in various body fluids like blood, plasma, saliva, and urine, making them accessible for non-invasive biomarker analysis. In addition, circRNAs can act as microRNA (miRNA) sponges, interact with RNA-binding proteins (RBPs), and even be translated into proteins, influencing various cellular processes and disease pathways.

Selected references

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Hyunjin Jeong, Suhyeon Son, Gyunghee Lee, Jae H Park, Siuk Yoo, Biogenesis of circular RNAs in vitro and in vivo from the Drosophila Nk2.1/scarecrow gene, G3 Genes|Genomes|Genetics, Volume 15, Issue 5, May 2025, jkaf055, [Oxford Academic]

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Zhang Y, Zhao Y, Ao X, Yu W, Zhang L, Wang Y, Chang W. The Role of Non-coding RNAs in Alzheimer's Disease: From Regulated Mechanism to Therapeutic Targets and Diagnostic Biomarkers. Front Aging Neurosci. 2021 Jul 2;13:654978. [PMC]

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