Circular RNAs: A New Piece in the Colorectal Cancer Puzzle

SIMPLE SUMMARY: Circular RNAs (circRNAs) are a relatively new and unexplored RNA type, implicated in several aspects of cell life, in normal and pathological states. This review aims to discuss the roles of circRNAs in colorectal cancer (CRC) initiation, progression, and therapy resistance, as well as their potential clinical value as CRC biomarkers. CRC is characterized by an elevated mortality rate, poor prognosis of high-grade tumors, high metastatic potential, and resistance to conventional therapies. Therefore, there is an urgent need for identification of novel molecules involved in colorectal carcinogenesis. Prompted by several studies examining circRNA involvement in CRC, in this review we seek to summarize the existing knowledge on circRNA expression in CRC and their implication in cellular pathways and molecular mechanisms underlying colorectal carcinogenesis. Lastly, we discuss the limitations and future perspectives highlighting the missing pieces of the puzzle and aspects of the circRNA research field that should be further investigated. ABSTRACT: Colorectal cancer (CRC) is the third most fatal type of malignancy, worldwide. Despite the advances accomplished in the elucidation of its molecular base and the existing CRC biomarkers introduced in the clinical practice, additional research is required. Circular RNAs (circRNAs) constitute a new RNA type, formed by back-splicing of primary transcripts. They have been discovered during the 1970s but were characterized as by-products of aberrant splicing. However, the modern high-throughput approaches uncovered their widespread expression; therefore, several questions were raised regarding their potential biological roles. During the last years, great progress has been achieved in the elucidation of their functions: circRNAs can act as microRNA sponges, transcription regulators, and interfere with splicing, as well. Furthermore, they are heavily involved in various human pathological states, including cancer, and could serve as diagnostic and prognostic biomarkers in several diseases. Particularly in CRC, aberrant expression of circRNAs has been observed. More specifically, these molecules either inhibit or promote colorectal carcinogenesis by regulating different molecules and signaling pathways. The present review discusses the characteristics and functions of circRNA, prior to analyzing the multifaceted role of these molecules in CRC and their potential value as biomarkers and therapeutic targets.