Circular RNAs (circRNAs) as novel diagnostic biomarkers for different diseases

Abstract

Introduction: Circular RNAs (circRNAs) are a novel class of endogenous noncoding RNAs and a field of much research interest and activity. In contrast linear RNAs, such as mRNAs, microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), circRNAs are distinguished by a closed loop structure which is covalently formed by back-splicing process. Since 1970s, circRNA molecules were first discovered in RNA viruses, they have emerged as interesting biomolecules because of their high abundance, stability, specificity and conservation. Description: circRNAs have been reported to modulate gene expression post-transcriptionally by acting as miRNAs sponges or cooperating with RNA binding proteins (RBPs). Tissue-specific regulation of circRNAs expression has been found associated with initiation and progression of lots of diseases, including various kinds of cancers, cardiovascular diseases and neurological disorders. Up to now, circRNAs are candidate as biomarkers for different types of cancers, including colorectal, lung, breast, gastric, hepatocellular carcinoma liver and pancreatic cancers. Also, their potential utility as biomarkers for cardiovascular diseases, neurological disorders, diabetes, rheumatoid arthritis, pulmonary tuberculosis and different ocular diseases has been proposed. Discussion and conclusion: There are several advantages to employing circRNAs as disease biomarkers. Firstly, circRNAs structure with a covalently closed, continuous loop instead of polyadenylation tail makes them more resistant to exonucleases. Secondly, they can be easily detected in body fluid of patients as plasma, serum, saliva, urine and semen and they could serve as non-invasive biomarkers. Thirdly, as shown than circRNAs indicate stage-specific manner during cancer progression, compared to common carbohydrate antigens; their expression levels may be a better indicator of cancer dynamics. Despite recent advances in characterizing circRNAs in human diseases, their clinical application need to deeper understanding of molecular features. Developing bioinformatics and experimental methods including deep sequencing might led to usage of circRNAs as novel powerful biomarkers in combination with current ones.