New insight into circRNAs: characterization, strategies, and biomedical applications

Abstract

Circular RNAs (circRNAs) are a class of covalently closed, endogenous ncRNAs. Most circRNAs are derived from exonic or intronic sequences by precursor RNA back-splicing. Advanced high-throughput RNA sequencing and experimental technologies have enabled the extensive identification and characterization of circRNAs, such as novel types of biogenesis, tissue-specific and cell-specific expression patterns, epigenetic regulation, translation potential, localization and metabolism. Increasing evidence has revealed that circRNAs participate in diverse cellular processes, and their dysregulation is involved in the pathogenesis of various diseases, particularly cancer. In this review, we systematically discuss the characterization of circRNAs, databases, challenges for circRNA discovery, new insight into strategies used in circRNA studies and biomedical applications. Although recent studies have advanced the understanding of circRNAs, advanced knowledge and approaches for circRNA annotation, functional characterization and biomedical applications are continuously needed to provide new insights into circRNAs. The emergence of circRNA-based protein translation strategy will be a promising direction in the field of biomedicine.

Blockade of the lncRNA-DOT1L-LAMP5 axis enhances autophagy and promotes degradation of MLL fusion proteins

“…Several lncRNAs with unique expression patterns have been reported to play essential roles in various cellular and molecular mechanisms driving carcinogenesis [ 11 , 13 , 34 , 49 ]. For example, HOTAIR is frequently overexpressed in breast cancer and has been shown to promote cell growth and migration by modulating multiple signaling pathways, including FGFR and Wnt/catenin pathways; while can also facilitate the invasiveness and metastasis of breast cancer by stimulating gene expression via the targeting of PRC2 and reducing Akt/JNK signaling pathway [ 18 , 19 ].…”

SKA3 targeted therapies in cancer precision surgery: bridging bench discoveries to clinical applications – review article

“…Circular RNAs (circRNAs) are a new type of noncoding RNAs that form a continuous closed loop structure, lacking both 5’ caps and 3’ tails 79 . Typically, circRNA is generated through a process of back-splicing, which involves the formation of a closed RNA transcript by joining the ends of a pre-mRNA molecule 80 , 81 . circRNA is formed when a downstream 5’ splice site (splice donor) in a pre-mRNA molecule joins with an upstream 3’ splice site (splice acceptor) in the same molecule through a noncanonical splicing event.…”

Circular RNAs and cervical cancer: friends or foes? A landscape on circRNA-mediated regulation of key signaling pathways involved in the onset and progression of HPV-related cervical neoplasms

“…Moreover, the CRISPR-Cas13 system has been shown to have a better performance in circRNA knockdown in terms of efficiency and specificity and is increasingly used to target circRNA without interfering with mRNA. However, there are still some problems with low delivery of gRNA and Cas13 enzyme into target cells, which need to be solved before CRISPR-Cas13 technology can be truly applied in clinic [ 200 , 201 ].…”