Regulation of microRNAs function by circular RNAs in human cancer.

Chao Han,Francis J Hornicek,Nicole A Seebacher,Quancheng Kan,Zhenfeng Duan

doi:10.18632/oncotarget.19930

Chao Han, Francis J Hornicek + Show 3 more

Open Access

https://doi.org/10.18632/oncotarget.19930

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Abstract

Circular RNAs (circRNAs) are a newly validated class of endogenous non-coding RNA, generated from the ligation of exons, introns, or both, which arise via a diverse number of cellular mechanisms. Due to rapid advances in the development of combined high-throughput sequencing and bioinformatics analyzing tools, many circRNAs have recently been discovered, revealing an expansive number of ubiquitously expressed mammalian circRNAs. Interestingly, it has recently been confirmed that circRNAs bind to microRNAs (miRs), as miR “sponges”, acting to suppress miR function. As miRs are known to alter the development and progression of cancer, circRNAs may offer a novel diagnostic and prognostic biomarker for cancer. Indeed, recent evidence has shown that circRNAs are associated with many human cancers. Herein, we review the molecular characteristics and biogenesis of circRNAs, with a focus on newly identified circRNAs that may play an important role in human cancer, through their regulation of miR expression.

Highlights

Circular RNAs have recently been identified as naturally occurring alternative RNA splicing products, which can inhibit the expression of microRNAs in eukaryotic cells [1,2,3,4]
Studies have highlighted the importance of circRNA dysregulation in a multitude of human cancers
CircRNAs represent a novel class of diverse endogenous RNAs that regulate miR expression through harboring miR response elements (MREs). This circRNA-miR interaction can act by regulating downstream transcriptional activity of miR target genes

Summary

Introduction

Circular RNAs (circRNAs) have recently been identified as naturally occurring alternative RNA splicing products, which can inhibit the expression of microRNAs (miRs) in eukaryotic cells [1,2,3,4]. The circRNA, circRNA-ITCH (cir-ITCH), has been reported to play an important role in inhibiting lung cancer progression, by functioning as an miR sponge of mulitple oncogenic miRs. This acts to enhance the expression of E3 ubiquitin-protein ligase (ITCH) and suppress activation of Wnt/β-catenin signaling, which is an important pathway involved in the process of cellular proliferation and migration.

Results

Conclusion