Abstract
Circular RNAs (circRNAs) are covalently closed RNA molecules in eukaryotes with features of high stability, tissue-specific and cell-specific expression. According to their biogenesis, circRNAs are mainly classified into five types, i.e. exonic circRNAs (EciRNAs), exon-intron circRNAs (EIciRNAs), intronic RNAs (CiRNAs), fusion circRNAs (f-circRNAs), and read-through circRNAs (rt-circRNAs). CircRNAs have been emerging as important non-coding regulatory RNAs in a variety of human cancers. CircRNA4s were revealed to exert regulatory function through multiple mechanisms, such as sponges/decoys of miRNAs and proteins, enhancers of protein functions, protein scaffolds, protein recruitment, or protein translation templates. Furthermore, some circRNAs are intensively associated with immune cells in tumor immune microenvironment (TIME), e.g. circARSP91 and natural killer cells. Through regulating immune checkpoint genes, circRNAs are demonstrated to modulate the immune checkpoint blockade immunotherapy, e.g. circCPA4 could up-regulate PD-L1 expression. In summary, we reviewed the molecular features of circRNAs and mechanisms how they exert functions. We further summarized functional implications of circRNA regulations in tumor immunology and immunotherapy. Further understanding of the regulatory roles of circRNAs in tumor immunology and immunotherapy will benefit tumor treatment.
Highlights
Circular RNAs are single-stranded circularized RNA molecules produced from back-splicing
CircRNA Classification Most circRNAs are generated from protein-coding genes, which are processed in the exon skipping during pre-messenger RNA transcription to form a lariat structure containing single or multiple exons
Other studies indicated that myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophage cells (TAMs) could produce arginase-1, inducible nitric oxide synthase and reactive oxygen species (ROS) to suppress the proliferation of T cells within the tumor
Summary
Circular RNAs (circRNAs) are single-stranded circularized RNA molecules produced from back-splicing. Accumulating evidence has shown that circRNA dysregulations are involved in a variety of human disorders, including viral infection [1], cardiac fibrosis [2], diabetes [3], and cancer [4]. Advances in high-throughput sequencing technologies and computational algorithms have driven the systematic detection and investigation of circRNAs. Through diverse mechanisms, circRNAs have shown important roles in tumor immunology and immunotherapy. We summarized the molecular characteristics of circRNAs and how they exert functions through various mechanisms. We further reviewed and discussed the prospective of circRNAs utilities in tumor immunology and immunotherapy
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