Abstract
Circular RNAs (circRNAs) are a novel class of noncoding RNAs, which are mainly formed as a loop structure at the exons caused by noncanonical splicing; they are much more stable than linear transcripts; recent reports have suggested that the dysregulation of circRNAs is associated with the occurrence and development of diseases, especially various human malignancies. Emerging evidence demonstrated that a large number of circRNAs play a vital role in a series of biological processes such as tumor cell proliferation, migration, drug resistance, and immune escape. Additionally, circRNAs were also reported to be potential prognostic and diagnostic biomarkers in cancers. In this work, we systematically summarize the biogenesis and characteristics of circRNAs, paying special attention to potential mechanisms and clinical applications of circRNAs in urological cancers, which may help develop potential therapy targets for urological cancers in the future.
Highlights
Plentiful researches have delineated sophisticated regulatory networks formed by diverse RNA species, including protein-coding messenger RNAs and noncoding RNAs represented by circular RNAs and microRNAs (Tay et al, 2011; Luigi et al, 2018; Xu et al, 2019; Zhao Q. et al, 2020; Vitiello et al, 2020)
As rising stars in noncoding RNAs, circRNAs have attracted more and more attention from researchers all over the world. They were traditionally considered as nonfunctional “genomic junks” generated by abnormal splicing events and until specific-expressed circRNA in Abbreviations: AR, androgen receptor; AUC, area under the curve; bladder cancer (BC), Bladder cancer; ceRNAs, competing endogenous RNAs; ciRNAs, circular intronic RNAs; CRPC, castration-resistant prostate cancer; ElciRNAs, exon-intron circRNAs; FN1, fibronectin 1; MREs, miRNA response elements; PCa, Prostate cancer; renal cell carcinoma (RCC), Renal cell carcinoma
Splicing sites within the circRNAs will generate three novel circRNAs, including intron retention, alternative 5′ and 3’ splicing circRNAs, unlike conventional back-splicing (Zhang et al, 2016) (Figure 1D). When it comes to the classification of circRNAs, we generally focus on the components of them, and the circRNAs can be divided into three types: 1) exonic circRNAs, they are mainly generated in the nucleus and exported to the cytoplasm; they can function as sponges for diverse miRNAs and proteins (Chen et al, 2015). 2) ciRNAs, are almost nonfunctional and distributed in the nucleus (Li X. et al, 2021). 3) exon–intron circRNAs (ElciRNAs), found to interact with small nuclear ribonucleoproteins and bind to RNA polymerase II to regulate gene transcription (Li Z. et al, 2015)
Summary
Plentiful researches have delineated sophisticated regulatory networks formed by diverse RNA species, including protein-coding messenger RNAs (mRNAs) and noncoding RNAs represented by circular RNAs (circRNAs) and microRNAs (Tay et al, 2011; Luigi et al, 2018; Xu et al, 2019; Zhao Q. et al, 2020; Vitiello et al, 2020). Some circRNAs have been reported to regulate RCC through affecting PI3K/AKT/mTOR signaling, which is involved in tumor proliferation, migration, and apoptosis, including activator circHIPK3 and inhibitor hsa-circ-0072309 (Chen T. et al, 2019).
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