Biological functions, mechanisms, and clinical significance of circular RNA in pancreatic cancer: a promising rising star

Abstract

Pancreatic cancer (PC) is a highly malignant solid tumor with insidious onset and easy early metastasis. Despite tremendous efforts devoted to research in this field, the mechanisms underlying PC tumorigenesis and progression remain unclear. Additionally, robust biomarkers and satisfactory therapeutic strategies for clinical use in PC patients are still lacking. Circular RNAs (circRNAs) are a new type of non-coding RNA originating from precursor messenger RNAs, with a covalent continuous closed-loop structure, strong stability and high specificity. Accumulating evidence suggests that circRNAs may participate in PC development and progression. Abnormal expression of circRNAs in PC is considered a vital factor that affects tumor cell proliferation, migration, invasion, apoptosis, angiogenesis and drug resistance. In this review of relevant articles published in recent years, we describe the basic knowledge concerning circRNAs, including their classification, biogenesis, functions and research approaches. Moreover, the biological roles and clinical significance of circRNAs related to PC are discussed. Finally, we note the questions remaining from recent studies and anticipate that further investigations will address these gaps in knowledge in this field. In conclusion, we expect to provide insights into circRNAs as potential targets for specific PC diagnosis and treatment in the future.

Keywords: Biomarker; Cancer diagnosis and therapy; CircRNAs; Pancreatic cancer.

Fig. 1

Biogenesis mechanism and functions of circular RNAs (circRNAs). Biogenesis of circRNAs. CircRNAs are generated from the 5’ splice donor site and 3’ splice acceptor site of precursor mRNAs (pre-mRNAs), which are covalently linked in reverse order. Lariat-driven circularization and intron-pairing-driven circularization are common models of circRNA formation. Additionally, some RNA binding proteins (RBPs) might act as regulatory activators or inhibitors in circRNA biogenesis. In terms of type, circRNAs can be sorted into three main categories: a) exonic circRNAs (EcRNAs), b) exon–intron circRNAs (EIciRNAs), and c) circular intronic RNAs (ciRNAs). The functions of circRNAs are as follows: (1) to compete with conventional splicing, (2) to act as transcriptional modulators, (3) to serve as translation templates of proteins, (4) to act as competing endogenous RNAs (ceRNAs), and (5) to bind to proteins

Fig. 2

Functional role of PC-related circRNAs. CircRNAs are associated with the hallmarks of PC. The red markers indicate upregulated circRNAs, while the purple markers indicate downregulated circRNAs

Fig. 3

The specific mechanism of circRNAs in the proliferation, cell cycle, and apoptosis of PC cells

Fig. 4

The specific mechanism of circRNAs in the migration, invasion, angiogenesis, and metastasis of PC cells