Circles reshaping the RNA world: from waste to treasure

Abstract

A new type of RNAs was identified from genes traditionally thought to express messenger or linear ncRNA (noncoding RNA) only. They were subsequently named as circRNAs (circular RNAs) due to the covalently closed structure. Accumulating studies were performed to explore the expression profile of circRNAs in different cell types and diseases, the outcomes totally changed our view of ncRNAs, which was thought to be junk by-products in the process of gene transcription, and enriched our poor understanding of its underlying functions. The expression profile of circRNAs is tissue-specific and alters across various stages of cell differentiation. The biological function of circRNAs is multi-faceted, involving five main features (sponge effect, post-transcriptional regulation, rolling circle translation, circRNA-derived pseudogenes and splicing interference) and varying differently from the locations, binding sites and acting modes of circRNAs. The regulating role of circRNAs is not isolated but through an enormous complicated network involving mRNAs, miRNAs and proteins. Although most of the potential functions still remain unclear, circRNAs have been proved to be ubiquitous and critical in regulating cellular processes and diseases, especially in cancers, from the laboratory to the clinic. Herein, we review circRNAs’ classification, biogenesis and metabolism, their well-studied and anticipated functions, the current understanding of the potential implications of circRNAs in tumorigenesis and cancer targeted therapy.

Circular RNA Expression Profiles Alter Significantly in Mouse Brain After Transient Focal Ischemia

“…~13% of the protein-coding genes form both linear RNAs and circular RNAs and they are highly conserved. 2,10,12 The mechanisms of actions of circRNAs under normal physiologic conditions are still being discovered, and their significance in protecting or damaging brain after an injury is not yet studied in detail. However, as circRNAs are known to regulate the expression of their host as well as neighboring genes, 42,43 their disruption can modulate many molecular events essential to protect the brain after stroke.…”

“…12 Furthermore, altered levels of specific circRNAs were thought to promote cancer, cardiac hypertrophy, atherosclerosis and neurodegenerative diseases. 13–17 To understand if stroke influences the expression of circRNAs, we profiled the levels of 14,236 circRNAs in the cerebral cortex of adult mice as a function of reperfusion time after transient focal ischemia.…”

Integrative analysis of circRNAs acting as ceRNAs involved in ethylene pathway in tomato

“…In general, circRNAs are formed through 3′–5′ ligation of a single RNA molecule, which can arise from exons, introns as well as intergenic regions and the expression of circRNAs are often cell, tissue and developmental‐stage specific (Salzman et al , , Memczak et al , Zhang et al ). CircRNAs can arise from alternative splicing, intron‐pairing‐driven circularization or lariat‐driven circularization and protein factors associated circulation (Liu et al ). Recently, a large number of circRNAs have been identified in Archaea, Caenorhabditis elegans , mice and humans (Danan et al , Salzman et al , , Memczak et al , Zhang et al ).…”

Overexpression of circular RNA circ‐CDC45 facilitates glioma cell progression by sponging miR‐516b and miR‐527 and predicts an adverse prognosis

“…5,6 Accumulating evidence indicates that circRNA is a promising biomarker in cancer due to its stability and specificity. 5,6 Accumulating evidence indicates that circRNA is a promising biomarker in cancer due to its stability and specificity.…”

“…5 The rapid development of RNA genomics has highlighted the oncogenic or anti-oncogenic role of circRNAs in many cancers, especially in GM. 5 The rapid development of RNA genomics has highlighted the oncogenic or anti-oncogenic role of circRNAs in many cancers, especially in GM.…”