A review of circular RNAs in colorectal cancer: insights into biomarker discovery and therapeutic targeting

Abstract

Colorectal cancer (CRC) is one of the most common cancers, with an incidence that has increased significantly over the last 20 years. The World Health Organization (WHO), under its cancer program, identifies CRC as the third most prevalent cancer worldwide with a high mortality rate, especially in patients under the age of 50. Despite advances in surgery, chemotherapy, radiotherapy, and molecular targeted therapy, CRC shares a low survival rate and poor prognosis due to late diagnosis. To address these challenges, research into alternative diagnostic and therapeutic strategies has increasingly focused on molecular mechanisms, including noncoding RNAs (ncRNAs). Circular RNAs (circRNAs), a subclass of endogenous ncRNAs characterized by their covalently enclosed loop structure, demonstrate greater stability than linear RNAs, making them potential candidates for clinical applications. The circRNAs possess differential expressions in cancers and function as tumor suppressive or oncogenic activities. This review discusses the recent findings on circRNAs and their potential for biomarkers and therapeutic targets in CRC. As circRNAs can serve as miRNA sponges, increase or decrease mRNA expression, and function to regulate an oncogenic or tumor suppressor pathway, there may be the possibility for an early diagnosis, prognosis, or therapeutic role of circRNAs in CRC. Highlighting the clinical implications of circRNAs, this review discusses their potential to transform current CRC management strategies and address critical gaps in timely diagnosis and effective treatment. It also emphasized the need for further clinical research to validate their utility and translate these findings into practice.

Keywords: biomarker; circular RNA; colorectal cancer; diagnosis; miRNA sponges; noncoding RNA; prognosis.

Figure 1

Functional roles of circRNAs in cellular processes.

Figure 2

Mechanisms of circRNA biogenesis. CircRNAs are formed through the back-splicing of precursor mRNA via RNA-binding proteins, intron pairing, or lariat-driven circularization.

Figure 3

Canonical and non-canonical splicing pathways. Pre-mRNA undergoes canonical splicing to form linear mRNA, or non-canonical splicing to generate circRNAs such as EciRNA, ElciRNA, and CiRNA via different circularization mechanisms.

Figure 4

Workflow for circRNA biomarker discovery. The process begins with sample collection and RNA extraction, followed by circRNA profiling using RNA-Seq or circRNA microarrays. Candidate biomarkers are identified and evaluated clinically, leading to the development of diagnostic tools.