Emerging role of circRNAs in cancer under hypoxia

Circular RNA (circRNA), a recently identified type of non-coding RNAs (ncRNAs), forms a covalently closed loop with neither a 5′ cap structure nor a 3′ polyadenylated tail. Due to their lack of free ends, circRNAs are not easily cleaved by RNase R, thus avoiding degradation and being more stable than linear RNAs. Recent studies have suggested that circRNAs play a crucial role in regulating gene expression by acting as microRNAs sponges, RNA binding protein sponges and translational regulators. Currently, circRNAs are hot research topics due to their close association with the development of cancer and other diseases. Hypoxia is the most common microenvironment during tumor growth, and hypoxia-inducible factors have different effects on tumor growth and influence important cancer characteristics, including cell proliferation, apoptosis, differentiation, vascularization/angiogenesis, genetic instability, tumor metabolism, tumor immune response, invasion and metastasis. The present review aimed to study the biogenesis and mechanisms of gene regulation of circRNAs in hypoxia, to summarize the latest studies on circRNAs as potential diagnostic and prognostic biomarkers in hypoxia, and to understand the role of circRNAs in the process of tumor drug resistance under hypoxia.