Functions and clinical significance of circular RNAs in glioma

Sun, Jikui; Li, Banban; Shu, Chang; Ma, Quanfeng; Wang, Jinhuan

doi:10.1186/s12943-019-1121-0

Cited by 143 publications

(103 citation statements)

References 160 publications

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“…Hence, circRNAs lack a 5′-cap and 3′-polyA tail, which makes them resistant to RNase R treatment. CircRNAs exert their biological functions during cellular processes, including acting as miRNA and protein sponges and modulating parental gene transcription and protein translation [29,30].…”

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: CircTLK1 promotes the proliferation and metastasis of renal cell carcinoma by sponging miR-136-5p

et al. 2020

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Background: Circular RNAs (circRNAs), a novel type of noncoding RNA (ncRNA), are covalently linked circular configurations that form via a loop structure. Accumulating evidence indicates that circRNAs are potential biomarkers and key regulators of tumor development and progression. However, the precise roles of circRNAs in renal cell carcinoma (RCC) remain unknown. Methods: Through circRNA high-throughput sequencing of RCC cell lines, we identified the circRNA TLK1 (circTLK1) as a novel candidate circRNA derived from the TLK1 gene. qRT-PCR detected the mRNA, circRNA and miRNA expression levels in RCC tissues and cells. Loss-of function experiments were executed to detect the biological roles of circTLK1 in the RCC cell phenotypes in vitro and in vivo. RNA-FISH, RNA pull-down, dual-luciferase reporter, western blot and immunohistochemistry assays were used to investigate the molecular mechanisms underlying the functions of circTLK1. Results: circTLK1 is overexpressed in RCC, and expression is positively correlated with distant metastasis and unfavorable prognosis. Silencing circTLK1 significantly inhibited RCC cell proliferation, migration and invasion in vitro and in vivo. circTLK1 was mainly distributed in the cytoplasm and positively regulated CBX4 expression by sponging miR-136-5p. Forced CBX4 expression reversed the circTLK1 suppression-induced phenotypic inhibition of RCC cells. Moreover, CBX4 expression was positively correlated with VEGFA expression in RCC tissues. CBX4 knockdown significantly inhibited VEGFA expression in RCC cells. Conclusion: Collectively, our findings demonstrate that circTLK1 plays a critical role in RCC progression by sponging miR-136-5p to increase CBX4 expression. circTLK1 may act as a diagnostic biomarker and therapeutic target for RCC.

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Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: CircTLK1 promotes the proliferation and metastasis of renal cell carcinoma by sponging miR-136-5p

et al. 2020

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“…Accumulating evidence has recently indicated that there are numerous circRNAs expressed in neuronal tissues, and that dysregulation of circRNAs can lead to diseases of the nervous system, including glioma [35]. The detailed regulatory molecular mechanisms of circRNAs include direct transcription and translation into functional proteins, transcriptional, and splicing regulation as well as miRNAs and RBP sponges [21,27,36].…”

Section: Discussionmentioning

confidence: 99%

The U2AF2 /circRNA ARF1/miR-342–3p/ISL2 feedback loop regulates angiogenesis in glioma stem cells

Jiang

Zhou

Zhao

et al. 2020

J Exp Clin Cancer Res

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Background Glioma is the most common and lethal primary brain tumor in adults, and angiogenesis is one of the key factors contributing to its proliferation, aggressiveness, and malignant transformation. However, the discovery of novel oncogenes and the study of its molecular regulating mechanism based on circular RNAs (circRNAs) may provide a promising treatment target in glioma. Methods Bioinformatics analysis, qPCR, western blotting, and immunohistochemistry were used to detect the expression levels of ISL2, miR-342–3p, circRNA ARF1 (cARF1), U2AF2, and VEGFA. Patient-derived glioma stem cells (GSCs) were established for the molecular experiments. Lentiviral-based infection was used to regulate the expression of these molecules in GSCs. The MTS, EDU, Transwell, and tube formation assays were used to detect the proliferation, invasion, and angiogenesis of human brain microvessel endothelial cells (hBMECs). RNA-binding protein immunoprecipitation, RNA pull-down, dual-luciferase reporter, and chromatin immunoprecipitation assays were used to detect the direct regulation mechanisms among these molecules. Results We first identified a novel transcription factor related to neural development. ISL2 was overexpressed in glioma and correlated with poor patient survival. ISL2 transcriptionally regulated VEGFA expression in GSCs and promoted the proliferation, invasion, and angiogenesis of hBMECs via VEGFA-mediated ERK signaling. Regarding its mechanism of action, cARF1 upregulated ISL2 expression in GSCs via miR-342–3p sponging. Furthermore, U2AF2 bound to and promoted the stability and expression of cARF1, while ISL2 induced the expression of U2AF2, which formed a feedback loop in GSCs. We also showed that both U2AF2 and cARF1 had an oncogenic effect, were overexpressed in glioma, and correlated with poor patient survival. Conclusions Our study identified a novel feedback loop among U2AF2, cARF1, miR-342–3p, and ISL2 in GSCs. This feedback loop promoted glioma angiogenesis, and could provide an effective biomarker for glioma diagnosis and prognostic evaluation, as well as possibly being used for targeted therapy.

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“…The findings mentioned above provided an important molecular and theoretical basis for the tissue-and disease-specific expression patterns of circRNAs. Moreover, studies on the correlation between the differential expression of circRNAs and the pathological grade or prognosis of glioma also confirmed the tissue specificity (41,42).…”

Section: Circrna Expression In Gliomasmentioning

confidence: 69%

Advances in circular RNAs and their role in glioma (Review)

et al. 2020

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Glioma is the most common primary tumour of the central nervous system, and is associated with a high postoperative recurrence rate and resistance to chemotherapy. High-grade glioblastoma in particular has a very poor prognosis and poses a serious threat to human health. Related studies have confirmed that the occurrence and development of gliomas are closely associated with the abnormal expression and regulation of genes. Moreover, the number of studies on the association of the expression of non-coding RNAs [linear RNAs, microRNAs and circular RNAs (circRNAs)] in human cells with glioma has been gradually increasing in recent years. Among those, circRNAs, previously considered to be 'splicing errors', have been shown to be highly expressed in eukaryotic cells and regulate the biological behaviour of gliomas. circRNAs are highly abundant and stable, and have become a research hotspot in the field of glioma molecular biology. The aim of the present review was to focus on the research progress regarding the association between circRNA expression and gliomas, and to provide a theoretical basis according to the currently available literature for further exploring this association. The present study may be of value for the early diagnosis, pathological grading, targeted therapy and prognostic evaluation of gliomas.

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Functions and clinical significance of circular RNAs in glioma

Cited by 143 publications

References 160 publications

RETRACTED ARTICLE: CircTLK1 promotes the proliferation and metastasis of renal cell carcinoma by sponging miR-136-5p

RETRACTED ARTICLE: CircTLK1 promotes the proliferation and metastasis of renal cell carcinoma by sponging miR-136-5p

The U2AF2 /circRNA ARF1/miR-342–3p/ISL2 feedback loop regulates angiogenesis in glioma stem cells

Advances in circular RNAs and their role in glioma (Review)

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