Functions and clinical significance of circular RNAs in acute myeloid leukemia

Abstract

Circular RNAs (circRNAs) are a class of covalently closed single-stranded RNA molecules. Four types of circRNAs have been reported in animal cells, and they have typical characteristics in their biogenesis, nuclear export and degradation. Advances in our understanding of the molecular functions of circRNAs in sponging microRNAs, modulating transcription, regulating RNA-binding proteins, as well as encoding proteins have been made very recently. Dysregulated circRNAs are associated with human diseases such as acute myeloid leukemia (AML). In this review, we focus on the recently described mechanisms, role and clinical significance of circRNAs in AML. Although great progress of circRNAs in AML has been achieved, substantial efforts are still required to explore whether circRNAs exert their biological function by other mechanisms such as regulation of gene transcription or serving as translation template in AML. It is also urgent that researchers study the machineries regulating circRNAs fate, the downstream effectors of circRNAs modulatory networks, and the clinical application of circRNAs in AML.

CircRNAs as New Therapeutic Entities and Tools for Target Identification in Acute Myeloid Leukemia

“…Knowledge on circRNA in AML with respect to their role as diagnostic and therapeutic biomarkers and from the point of view of mechanistic insights has been summarized in (2,27,28). In our review, we focus on their role as possible new therapeutic entities and as tools for target identification.…”

CircRNA: a rising star in leukemia

“…Most of the circRNAs exist in the cytoplasm, but a small fraction of circRNAs also exist in the nucleus, such as ciRNAs and ElciRNAs, suggesting that circRNAs may be involved in the transcriptional regulation of parental genes ( Fig. 1B ) ( Kumari et al, 2022 ; Li et al, 2020a ; Wang et al, 2020 ; Zhou et al, 2022b ). CiRNAs and ElciRNAs regulate gene transcription differently.…”

Editorial: Exploring circular RNAs and their applications within health and disease

“…CircRNAs are generated via back-splicing or exon skipping of pre-mRNAs, a complex process regulated by intronic repeats and RNA-binding proteins (RBPs) that differs from canonical splicing (Ebbesen et al, 2016). CircRNAs have been described in various subcellular fractions (nucleus, cytoplasm, exosome), and are more stable than their linear ncRNA counterparts, because their structures are not affected by RNA exonuclease RNase R (Robinson and Port, 2022).Although the functions of most circRNAs are not fully elucidated, emerging evidence demonstrate that dysregulated circRNAs play a key role in many biological processes as regulatory non-coding RNAs, by acting as microRNAs sponges, modulating splicing, transcription, chromatin modification, regulating RNA-binding proteins, as well as encoding proteins (Zhou et al, 2022). Their great stability, functional properties, and the presence in the circulation, make circRNAs not only a potential target but also therapeutic agents.…”

“…Although the functions of most circRNAs are not fully elucidated, emerging evidence demonstrate that dysregulated circRNAs play a key role in many biological processes as regulatory non-coding RNAs, by acting as microRNAs sponges, modulating splicing, transcription, chromatin modification, regulating RNA-binding proteins, as well as encoding proteins ( Zhou et al, 2022 ). Their great stability, functional properties, and the presence in the circulation, make circRNAs not only a potential target but also therapeutic agents.…”