Insights into the Evolving Roles of Circular RNAs in Cancer

Simple Summary The central dogma of RNA biology was traditionally governed by the transcription of DNA into messenger RNA (mRNA) followed by translation into protein. As additional functions of RNA were discovered, it became clear that there were many species of RNA, and many of those species were multifunctional with roles outside of coding for protein. One such area of discovery was the ability to form circular RNAs (circRNAs) that have been shown to be important in a wide range of cellular processes and as such are important in health and disease. These functions broadly include the modulation of gene expression, facilitation of protein-protein interactions and protein translation. It is important to understand how the dysregulation of these processes are involved in cancer progression and the avenues this may open for the targeting or overexpression of circRNAs as novel therapeutics. The majority of RNAs transcribed from the human genome have no coding capacity and are termed non-coding RNAs (ncRNAs). It is now widely accepted that ncRNAs play key roles in cell regulation and disease. Circular RNAs (circRNAs) are a form of ncRNA, characterised by a closed loop structure with roles as competing endogenous RNAs (ceRNAs), protein interactors and transcriptional regulators. Functioning as key cellular regulators, dysregulated circRNAs have a significant impact on disease progression, particularly in cancer. Evidence is emerging of specific circRNAs having oncogenic or tumour suppressive properties. The multifaceted nature of circRNA function may additionally have merit as a novel therapeutic target, either in treatment or as a novel biomarker, due to their cell-and disease-state specific expression and long-term stability. This review aims to summarise current findings on how circRNAs are dysregulated in cancer, the effects this has on disease progression, and how circRNAs may be targeted or utilised as future potential therapeutic options.