Role of circular RNAs in cardiovascular diseases

Abstract

Circular RNAs are important regulators of multiple biological processes such as organogenesis and oncogenesis. Although the bulk of concerning studies focused on revealing their diversified roles in various types of cancers, reports began to accumulate in cardiovascular field these days. We summarize circular RNAs implicated in cardiovascular diseases, aiming to highlight the advances in the knowledge of such diseases and their potential of being promising target for diagnosis and therapy.

Keywords: Circular RNA; biomarkers; cardiology; pathology; therapy; vascular.

Figure 1.

Schematic representation illustrating circRNA biogenesis. The generation of circRNAs can be attained via a direct backsplicing path, in which circularization is driven by intronic reverse complementary (IR) sequence (“intron pairing”) (a, b) or RNA-binding protein (RBP) pairing (c) that brings the sequences in proximity of each other to promote circularization. CircRNAs can also be formed through a lariat driven path characterized by a lariat structure whose flanking sequences facilitate the generation of circRNAs (d).

Figure 2.

Mechanism underlying how circRNA functions. (A) MiRNA sponge: harboring binding sites for certain miRNAs, circRNAs can affect miRNA-targeted gene expression by inhibition of target gene mRNA degradation. (B) Transcriptional control: exon–intron circRNAs (EIcircRNAs) regulate gene transcription in the nucleus mainly through binding to polymerase II (Pol II) and U1 snRNA. (C) Interaction with RBPs: circRNAs can interact with proteins through direct binding. For example, circFoxo binds to transcription factors like ID1, E2F1, and HIF-1a and therefore retain them in the cytoplasm. (D) Translation: some circRNAs may translate small peptides through a rolling circle amplification mechanism.