The interaction of circRNAs and RNA binding proteins: An important part of circRNA maintenance and function

Zang, Jiankun; Lu, Dan; Xu, Anding

doi:10.1002/jnr.24356

Cited by 448 publications

(311 citation statements)

References 62 publications

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“…4 Recently, accumulating evidence has indicated that circRNAs play a pivotal role in cancer progression by regulating gene expression at the levels of chromatin modification, transcriptional, and posttranscriptional regulation. [5][6][7] Several studies have found that dysfunction of various circRNAs is closely related to the proliferation, apoptosis, migration, invasion, and drug resistance of tumor cells. 5,[8][9][10] Therefore, circRNAs may represent potential biomarkers with diagnostic, prognostic, and therapeutic values in human carcinomas.…”

Section: Introductionmentioning

confidence: 99%

Retracted: Elevation of circular RNA circ‐POSTN facilitates cell growth and invasion by sponging miR‐1205 in glioma

Yang

Zhang

Chen³

et al. 2019

J of Cellular Biochemistry

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Glioma is the most common type of primary intracranial tumor. Dysregulation of circular RNAs (circRNAs) plays a critical role in multiple solid tumors. However, the expression profiles of circRNAs and their functions in glioma have been rarely studied. The current work aims to investigate the clinical significance of a novel circRNA, circ‐POSTN, in glioma and explore its biological functions and mechanisms in the progression of glioma. We found that circ‐POSTN was highly expressed in glioma tissue samples and cells. High circ‐POSTN expression was significantly linked to larger tumor size, higher World Health Organization grades, and shorter overall survival. Furthermore, silencing of circ‐POSTN in glioma cells could decrease cell growth, migratory and invasive potential, and induce cell apoptosis in LN229 cells. On the contrary, ectopically expressed circ‐POSTN induced the opposite effects in the U251 cell line. By bioinformatic prediction and luciferase reporter assay, we identified that miR‐1205 could be sponged by circ‐POSTN. Further rescue assays demonstrated that the oncogenic functions of circ‐POSTN are partly attributed to its regulation of miR‐1205 in glioma cells. Taken together, our data suggest that circ‐POSTN plays an oncogenic role in glioma progression and may serve as a novel therapeutic target in this deadly disease.

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Section: Introductionmentioning

confidence: 99%

Retracted: Elevation of circular RNA circ‐POSTN facilitates cell growth and invasion by sponging miR‐1205 in glioma

Yang

Zhang

Chen³

et al. 2019

J of Cellular Biochemistry

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“…On the other hand, circRNA is capable of physically interacting with RNA-binding protein to regulate gene expression. 25 Herein, we found that circ-CCND1 could directly bind to HuR to potentiate CCND1 mRNA stability. HuR is a well-known RNA-binding protein that prevents mRNA decay via targeting the uridylate-rich element (ARE, (A/U)UUU(A/U)) on the 3′-UTR.…”

Section: Discussionmentioning

confidence: 83%

“…On the other hand, circRNA is capable of physically interacting with RNA‐binding protein to regulate gene expression . Herein, we found that circ‐CCND1 could directly bind to HuR to potentiate CCND1 mRNA stability.…”

Section: Discussionmentioning

confidence: 86%

circRNA circ‐CCND1 promotes the proliferation of laryngeal squamous cell carcinoma through elevating CCND1 expression via interacting with HuR and miR‐646

Zang

Wan

et al. 2020

J Cellular Molecular Medi

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Cyclin D1 (CCND1) is a well‐known proliferation promoter that accelerates G1/S transition in cancer. However, the underlying mechanism by which CCND1 is regulated is still largely unknown. In this study, we identified a novel circular RNA (circRNA) derived from CCND1 (circ‐CCND1, hsa_circ_0023303) as a key regulator for CCND1. circ‐CCND1 was found to be markedly up‐regulated in laryngeal squamous cell carcinoma (LSCC) and closely associated with aggressive clinical features and adverse prognosis. Depletion of circ‐CCND1 significantly inhibited LSCC cell proliferation in vitro and retarded tumour growth in vivo. Regarding the mechanism, circ‐CCND1 physically bound to human antigen R (HuR) protein to enhance CCND1 mRNA stability; on the other hand, circ‐CCND1 could act as an effective sponge for miR‐646 to alleviate the repression of miR‐646 on CCND1 mRNA. As a result, circ‐CCND1 post‐transcriptionally elevated CCND1 expression via coordinated avoidance of CCND1 mRNA decay, thereby promoting LSCC tumorigenesis. Taken together, our findings uncover the essential proliferation‐promoting role of circ‐CCND1 through regulation of the stability of CCND1 mRNA in LSCC. Targeting circ‐CCND1 may be a promising treatment for LSCC patients.

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“…RNA transcription, pre-mRNA splicing and polyadenylation as well as modification, stability, localization, and translation of RNA (reviewed in (13) ). Recent studies have shown that RBPs also affect all phases of the circRNA lifecycle (reviewed in (14) ). Some RBPs are involved in circRNA biogenesis as has been shown for Quaking (QKI) (15) , FUS (16) , HNRNPL (17) , RBM20 (18) , and Muscleblind (19) , which bind to specific intronic RBP motifs and promote formation of some circRNAs in certain biological settings.…”

Section: Introductionmentioning

confidence: 99%

Transcriptome-wide profiles of circular RNA and RNA binding protein interactions reveal effects on circular RNA biogenesis and cancer pathway expression

Okholm

Sathe

Park

et al. 2020

Preprint

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Circular RNAs (circRNAs) are stable, often highly expressed RNA transcripts with potential to modulate other regulatory RNAs. A few circRNAs have been shown to bind RNA binding proteins (RBPs), however, little is known about the prevalence and strength of these interactions in different biological contexts. Here, we comprehensively evaluate the interplay between circRNAs and RBPs in the ENCODE cell lines, HepG2 and K562, by profiling the expression of circRNAs in fractionated total RNA-sequencing samples and analyzing binding sites of 150 RBPs in large eCLIP data sets. We show that KHSRP binding sites are enriched in flanking introns of circRNAs in both HepG2 and K562 cells, and that KHSRP depletion affects circRNA biogenesis. Additionally, we show that exons forming circRNAs are generally enriched with RBP binding sites compared to non-circularizing exons. To detect individual circRNAs with regulatory potency, we computationally identify circRNAs that are highly covered by RBP binding sites and experimentally validate circRNA-RBP interactions by RNA immunoprecipitations. We characterize circCDYL, a highly expressed circRNA with clinical and functional implications in bladder cancer, which is covered with GRWD1 binding sites. We confirm that circCDYL binds GRWD1 in vivo and functionally characterizes the effect of circCDYL-GRWD1 interactions on target genes in HepG2. Furthermore, we confirm interactions between circCDYL and RBPs in bladder cancer cells and demonstrate that circCDYL depletion affects hallmarks of cancer and perturbs the expression of key cancer genes, e.g. TP53 and MYC . Finally, we show that elevated levels of highly RBP-covered circRNAs, including circCDYL, are associated with overall survival of bladder cancer patients. Our study demonstrates transcriptome-wide and cell-type-specific circRNA-RBP interactions that could play important regulatory roles in tumorigenesis.

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The interaction of circRNAs and RNA binding proteins: An important part of circRNA maintenance and function

Cited by 448 publications

References 62 publications

Retracted: Elevation of circular RNA circ‐POSTN facilitates cell growth and invasion by sponging miR‐1205 in glioma

Retracted: Elevation of circular RNA circ‐POSTN facilitates cell growth and invasion by sponging miR‐1205 in glioma

circRNA circ‐CCND1 promotes the proliferation of laryngeal squamous cell carcinoma through elevating CCND1 expression via interacting with HuR and miR‐646

Transcriptome-wide profiles of circular RNA and RNA binding protein interactions reveal effects on circular RNA biogenesis and cancer pathway expression

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