Circular RNAs in eukaryotic cells: origin, characteristics, mechanisms of molecular functioning in human malignant diseases

Abstract

Circular RNAs (circRNAs) are an evolutionarily conserved novel class of non-coding endogenous RNAs (ncRNAs) found in the eukaryotic transcriptome, originally believed to be aberrant RNA splicing by-products with limited functionality. However, recent advances in highthroughput genomic technology have allowed circRNAs to be characterized in detail and revealed their important functions in controlling various biological and molecular processes, the most essential being gene regulation. Due to structural stability, high expression, availability of microRNA (miRNA) binding sites and tissue-specific expression, circRNAs have become hot topic of research in RNA 2 biology. Unlike linear RNAs, circRNAs are produced differentially by backsplicing exons or lariat introns from a pre-messenger RNA (mRNA) forming covalently closed loop-like molecules missing 3' poly-(A) tail or 5' cap structures, thus rendering them resistant to exonuclease-mediated degradation. Previous studies have revealed multiple roles of circRNAs as sponges for miRNA and RNA-binding proteins (RBP), as well as regulators of transcription, translation, and splicing events. Recent advances in the field suggest that the circRNAs are involved in many human disorders, including cancer and neurodegenerative disorders such as Alzheimers and Parkinsons disease, due to their aberrant expression in different pathological conditions. The circRNAs are stable in cells, owing to their circular structure. Participation of circRNAs in programmed cellular destruction by autophagy is discussed in details. The autophagy is a catabolic process which promotes decomposition and recycling of harmful or redundant biological macromolecules and initiates destruction of ageing cells. Processes how circRNAs influence a course of a disease, including an autophagy are in detail discussed, specifying that it joins at the beginning and upon development of various illnesses, and it can influence drug resistance (for example, antitumor efficiency of Cisplatin). The functional versatility exhibited by circRNAs enables them to serve as potential diagnostic or predictive biomarkers for various diseases. This review discusses the properties, characterization, profiling, and the diverse molecular actions of circRNAs and their usage as potential therapeutic targets in different human malignancies.