Circular RNAs as Potential Biomarkers in Breast Cancer

Abstract

Due to the high heterogeneity and initially asymptomatic nature of breast cancer (BC), the management of this disease depends on imaging together with immunohistochemical and molecular evaluations. These tests allow early detection of BC and patient stratification as they guide clinicians in prognostication and treatment decision-making. Circular RNAs (circRNAs) represent a class of newly identified long non-coding RNAs. These molecules have been described as key regulators of breast carcinogenesis and progression. Moreover, circRNAs play a role in drug resistance and are associated with clinicopathological features in BC. Accumulating evidence reveals a clinical interest in deregulated circRNAs as diagnostic, prognostic and predictive biomarkers. Furthermore, due to their covalently closed structure, circRNAs are highly stable and easily detectable in body fluids, making them ideal candidates for use as non-invasive biomarkers. Herein, we provide an overview of the biogenesis and pleiotropic functions of circRNAs, and report on their clinical relevance in BC.

Keywords: biomarker; breast cancer; circular RNA; circulating RNA; circulating circRNAs; diagnostic biomarker; long non-coding RNAs; microRNA; microRNA sponge; non-coding RNA.

Figure 1

CircRNA biogenesis and functions. (A) Circularization of circRNAs, including exonic, intronic, and exonic-intronic circRNAs, arises from pre-mRNA transcripts through different mechanisms of back-splicing. After formation, circRNAs are transported from the nucleus to the cytoplasm by RNA helicases (DDX39A, or DDX39B) in a size-dependent manner. (B) CircRNAs have different mechanisms of action. Indeed, they can interact with proteins, encode for proteins, and function as microRNA sponge (mainly). (C) CircRNAs can be further released into body fluids as cell-free circRNAs or enriched in extracellular vesicles (e.g., exosomes).