Disease-Associated Circular RNAs: From Biology to Computational Identification

Abstract

Circular RNAs (circRNAs) are endogenous RNAs with a covalently closed continuous loop, generated through various backsplicing events of pre-mRNA. An accumulating number of studies have shown that circRNAs are potential biomarkers for major human diseases such as cancer and Alzheimer’s disease. Thus, identification and prediction of human disease-associated circRNAs are of significant importance. To this end, a computational analysis-assisted strategy is indispensable to detect, verify, and quantify circRNAs for downstream applications. In this review, we briefly introduce the biology of circRNAs, including the biogenesis, characteristics, and biological functions. In addition, we outline about 30 recent bioinformatic analysis tools that are publicly available for circRNA study. Principles for applying these computational strategies and considerations will be briefly discussed. Lastly, we give a complete survey on more than 20 key computational databases that are frequently used. To our knowledge, this is the most complete and updated summary on publicly available circRNA resources. In conclusion, this review summarizes key aspects of circRNA biology and outlines key computational strategies that will facilitate the genome-wide identification and prediction of circRNAs.

Role of circRNA-miRNA-mRNA interaction network in diabetes and its associated complications

“…This review has summarized the circRNA-miRNA-mRNA interaction network in diabetes and its associated disorders. More than 20,000 novel circRNAs have been identified to date, 112 although only a few are identified with their regulatory pathways or interaction networks. The importance of identifying the interaction network between them is that it would shed light on the holistic and mechanistic picture of the regulation of various genes and their upstream elements in response to different pathological conditions.…”

Structural characterizations of a unusual peptide CORO1C-47aa encoded by circRNA hsa-circ-0000437 associated with endometrial cancer

“…The circular RNAs are associated with a number of different cellular activities. However, circular RNAs belong to the class of non-coding RNAs [1][2][3][4][5][6][7][8][9][10]. Surprisingly, the particular circular RNA, circ-0000437, has protein coding potentials and it codes for the peptide CORO1C-47aa.…”

“…Circular RNAs are covalently closed RNA molecules which belong to the class of noncoding RNAs. They are obtained by the method of backsplicing [1][2][3][4][5]. Initially, they were considered to be transcriptional junks.…”

“…Recent studies have revealed that the circular RNA molecules take part in numerous cellular activities like, Gene Expressions, Sponging of miRNAs, and Binding to proteins for the regulatory purposes to name a few [1][2][3][4][5][6][7][8][9][10]. As a matter of surprise, some of the circular RNAs have been found to be able to code for peptides/proteins having a variety of functionalities [11][12][13][14][15].…”

Comprehensive Analysis of RNA Expression Profile Identifies Hub miRNA-circRNA Interaction Networks in the Hypoxic Ischemic Encephalopathy

“…It has been shown that changes in the levels of specific circRNAs exhibited an association with carcinoma, ischemia, stroke, neurodegenerative diseases, heart disease, etc. [ 13 , 14 ]. CircRNAs, especially in brain tissue, were not only related to the nervous system's development, differentiation, and biological function but also functioned importantly in the dysfunction and pathology after brain damage [ 15 ].…”