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Review
. 2021 Feb 5:9:617281.
doi: 10.3389/fcell.2021.617281. eCollection 2021.

Insights Into the Role of CircRNAs: Biogenesis, Characterization, Functional, and Clinical Impact in Human Malignancies

Sabah Nisar  1 , Ajaz A Bhat  1 , Mayank Singh  2 , Thasni Karedath  3 , Arshi Rizwan  4 , Sheema Hashem  1 , Puneet Bagga  5 , Ravinder Reddy  6 , Farrukh Jamal  7 , Shahab Uddin  8 , Gyan Chand  9 , Davide Bedognetti  10   11   12 , Wael El-Rifai  13 , Michael P Frenneaux  14 , Muzafar A Macha  15 , Ikhlak Ahmed  3   3 , Mohammad Haris  1   16
Affiliations
Review

Insights Into the Role of CircRNAs: Biogenesis, Characterization, Functional, and Clinical Impact in Human Malignancies

Sabah Nisar et al. Front Cell Dev Biol. .

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 decreased functionality. However, recent advances in high-throughput genomic technology have allowed circRNAs to be characterized in detail and revealed their role in controlling various biological and molecular processes, the most essential being gene regulation. Because of the structural stability, high expression, availability of microRNA (miRNA) binding sites and tissue-specific expression, circRNAs have become hot topic of research in RNA biology. Compared to the linear RNA, circRNAs are produced differentially by backsplicing exons or lariat introns from a pre-messenger RNA (mRNA) forming a covalently closed loop structure missing 3' poly-(A) tail or 5' cap, rendering them immune to exonuclease-mediated degradation. Emerging research has identified multifaceted roles of circRNAs as miRNA and RNA binding protein (RBP) sponges and transcription, translation, and splicing event regulators. CircRNAs have been involved in many human illnesses, including cancer and neurodegenerative disorders such as Alzheimer's and Parkinson's disease, due to their aberrant expression in different pathological conditions. 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 mechanisms of circRNAs and their use as potential therapeutic targets in different human malignancies.

Keywords: RNA binding protein; circRNA; drug resistance; miRNA sponges; signaling pathways; tumor.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Biogenesis of circular RNA. The figure represents three different circular RNAs; Intron –exon, exon and intron circular RNAs, and its biogenesis mechanism during pre-mRNA splicing events. Intron pairing takes place with repeated inverted elements like Alu repeats, whereas lariat-driven biogenesis produces circRNAs during the exon skipping process. circRNAs can produce functional proteins that directly impact tumor progression (a few examples are shown in the box). circRNAs also act as protein sponges and are involved in protein recruitment.
FIGURE 2
FIGURE 2
circRNA synthesis. The circRNA is formed by a head-to-tail backsplice junction (BSJ) through a downstream splice donor to an upstream splice acceptor. Chimeric reads align at the BSJ, directly confirming the existence of this non-canonical splice junction. The mates of the chimeric read can align to either of the BSJ forming exons. Supportive reads align to the BSJ forming exons in an orientation that is divergent regarding the direction of transcription but becomes properly inward-facing and convergent for BSJ. Adapted from Ahmed et al. (2016).
FIGURE 3
FIGURE 3
Graphical representation of circRNAs dysregulation in different cancers.
See this image and copyright information in PMC

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References

    1. Abdelmohsen K., Panda A. C., Munk R., Grammatikakis I., Dudekula D. B., De S., et al. (2017). Identification of HuR target circular RNAs uncovers suppression of PABPN1 translation by CircPABPN1. RNA Biol. 14 361–369. 10.1080/15476286.2017.1279788 - DOI - PMC - PubMed
    1. Abe N., Hiroshima M., Maruyama H., Nakashima Y., Nakano Y., Matsuda A., et al. (2013). Rolling circle amplification in a prokaryotic translation system using small circular RNA. Angew. Chem. Int. Ed. Engl. 52 7004–7008. 10.1002/anie.201302044 - DOI - PubMed
    1. Abe N., Matsumoto K., Nishihara M., Nakano Y., Shibata A., Maruyama H., et al. (2015). Rolling circle translation of circular RNA in living human cells. Sci. Rep. 5:16435. - PMC - PubMed
    1. Ahmed I., Karedath T., Al-Dasim F. M., Malek J. A. (2019). Identification of human genetic variants controlling circular RNA expression. RNA 25 1765–1778. 10.1261/rna.071654.119 - DOI - PMC - PubMed
    1. Ahmed I., Karedath T., Andrews S. S., Al-Azwani I. K., Mohamoud Y. A., Querleu D., et al. (2016). Altered expression pattern of circular RNAs in primary and metastatic sites of epithelial ovarian carcinoma. Oncotarget 7 36366–36381. 10.18632/oncotarget.8917 - DOI - PMC - PubMed

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