Abstract
Circular RNAs (circRNAs) were discovered in the 1970s, but they have drawn increasing attention in recent years. Currently, we know that circRNAs are not “wrongly spliced” during transcription but play important roles in the initiation and development of various diseases, including cancers. Recently, a growing number of studies have suggested that cancer stem cells (CSCs) may contribute to the origination and maintenance of cancers. This review briefly introduces the major functions of circRNAs, including interacting with other noncoding RNAs, competing with pre-mRNA splicing, binding with proteins to form a scaffold, promoting protein nuclear translocation and even translating proteins in a cap-independent manner. Furthermore, we describe the regulatory mechanism of circRNAs in CSC phenotypes and discuss the potential clinical applications of circRNAs in CSC-targeted therapy, including functioning as new biomarkers, acting as vaccines and breaking the therapeutic resistance of CSCs. Finally, we discuss the major limitations and challenges in the field, which will be beneficial for the future clinical use of circRNAs.
Highlights
Cancer stem cells, a special subpopulation of cancer cells, exhibit self-renewal properties as well as high proliferation and multidirectional differentiation potential
It functions as a ceRNA to increase the expression of STAT5A, which induces stem-like cell properties and the epithelial-tomesenchymal transition and promotes the migration and invasion of CD133+CD44+ LCSCs [48, 49]
Clinical studies have shown that mRNA can be transfected into dendritic cells (DCs) and translated into proteins to function as antigens [65], meaning that circRNAs, especially those that can be translated into proteins, may function as potential antigens and activate CD8+ T cells in cancer stem cells (CSCs)-based vaccines (Figure 2B)
Summary
Reviewed by: Zexian Liu, Sun Yat-sen University Cancer Center (SYSUCC), China Barak Rotblat, Ben-Gurion University of the Negev, Israel. Circular RNAs (circRNAs) were discovered in the 1970s, but they have drawn increasing attention in recent years. We know that circRNAs are not “wrongly spliced” during transcription but play important roles in the initiation and development of various diseases, including cancers. This review briefly introduces the major functions of circRNAs, including interacting with other noncoding RNAs, competing with pre-mRNA splicing, binding with proteins to form a scaffold, promoting protein nuclear translocation and even translating proteins in a cap-independent manner. We describe the regulatory mechanism of circRNAs in CSC phenotypes and discuss the potential clinical applications of circRNAs in CSC-targeted therapy, including functioning as new biomarkers, acting as vaccines and breaking the therapeutic resistance of CSCs. we discuss the major limitations and challenges in the field, which will be beneficial for the future clinical use of circRNAs
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