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Review
. 2016 Jun 1;6(6):1167-76.
eCollection 2016.

Circular RNAs as potential biomarkers for cancer diagnosis and therapy (V体育安卓版)

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Review

Circular RNAs as potential biomarkers for cancer diagnosis and therapy

Fengling Wang et al. Am J Cancer Res. .

Abstract

Circular RNAs (circRNAs) are a naturally occurring type of universal and diverse endogenous noncoding RNAs which unlike linear RNAs, have covalently linked ends. They are usually stable, abundant, conserved RNA molecules and often exhibit tissue/developmental-stage specific expression. Functional circRNAs have been identified to act as microRNA sponges and RNA-binding protein (RBP) sequestering agents as well as transcriptional regulators. These multiple functional roles elicit a great potential for circRNAs in biological applications VSports手机版. Emerging evidence shows that circRNAs play important roles in several diseases, particularly in cancer where they act through regulating protein expression of the pivotal genes that are critical for carcinogenesis. The presence of abundant circRNAs in saliva, exosomes and clinical standard blood samples will make them potential diagnostic or predictive biomarkers for diseases, particularly for cancer development, progression and prognosis. Here, we review the current literature and provide evidence for the impact of circRNAs in cancers and their potential significance in cancer prognosis and clinical treatment. .

Keywords: RNA; cancer; circular RNA; expression; regulation V体育安卓版. .

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"V体育官网入口" Figures

Figure 1
Figure 1
Possible models of circRNAs biogenesis. A. Lariat-driven circularization. Exon skipping event results in circular RNA formation where the 3’ splice donor site of exon 1 covalently links to the 5’ splice acceptor of exon 4, forming a lariat structure containing the skipped exons 2 and 3 as well as an mRNA consisting of exons 1 and 4. This lariat is spliced internally, removing or retaining the intronic sequence to generate ecircRNA or EIciRNA. B. Intron-pairing-driven circularization. Direct base-pairing of the introns flanking inverted repeats or ALU elements forms a circular structure. The introns are removed or retained to form ecircRNA or EIciRNA. C. ciRNAs. The ciRNAs are generated from lariat introns that can escape debranching. GU-rich sequences near the 5’ splice site (blue box) and C-rich sequences near the branch point (red box) are sufficient for an intron to escape debranching and become a stable circRNA. D. RBP-driven circularization. Interactions between RBPs form a bridge between the flanking introns to facilitate the exon circulation. A circRNA or an EIciRNA is generated due to the retention of internal introns. E. Intergenic circRNA. ecircRNAs are always located in the cytoplasm, where they have extraordinary stability due to their resistance to RNA exonucleases. In contrast, ciRNAs and EIciRNAs are predominantly located in the nucleus.
Figure 2
Figure 2
A miR-7/ciRS-7/target gene regulatory network analyzed through CircNet database (http://circnet.mbc.nctu.edu.tw/). The ciRS-7/CDR1as is also named circ-CDR1-antisense.5 in the CircNet database.

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