The circRNA-microRNA code: emerging implications for cancer diagnosis and treatment

Abstract

Circular RNAs (circRNAs) comprise an emerging new class of endogenous RNAs expressed abundantly by the eukaryotic transcriptome. They are characterized by a covalently closed loop structure, resulting in RNA molecules that are more stable than linear RNAs. A growing number of studies indicate that circRNAs play critical roles in human diseases and show great potential as biomarkers and therapeutic targets. The molecular events determined by circRNA activity, the circRNA code, involve other types of noncoding RNA molecules, primarily microRNAs, long noncoding RNAs, and RNA-binding proteins. Herein, we mainly focus on the circRNA-microRNA code, showing how this relationship impacts the regulation of gene expression in cancer. The emerging roles for circRNAs in oncogenic pathways highlight new perspectives for the detailed molecular dissection of cancer pathogenesis and, at the same time, offer new opportunities to design innovative therapeutic strategies. Here, we review recent research advancements in understanding the biogenesis, molecular functions, and significance of circRNAs in cancer diagnosis and treatment.

Keywords: cancer; circRNA code; circular RNAs; microRNAs; patients.

Figure 1

Models proposed to explain the biogenesis of circRNAs. A schematic representation of the two models that generate circRNAs: left, the exon skipping or lariat intermediate model; right, the direct back‐splicing model.

Figure 2

Circular RNAs can affect the miRNA activity. (A) Schematic representation of miRNA mechanism of action. (B) Schematic representation of circRNAs acting as miRNAs sponge. Three examples of sponge‐like circRNAs are shown.

Figure 3

Cancer biomarkers and gene expression signatures. The noncoding part of the genome plays an important role in the regulation of gene expression in cancer (Harrow et al., 2012).