Circular RNAs: A novel type of biomarker and genetic tools in cancer

Han, Yineng; Xia, Sheng-Yuan; Zhang, Yuanyuan; Zheng, Junhua; Li, Wei

doi:10.18632/oncotarget.18350

Cited by 92 publications

(74 citation statements)

References 100 publications

(131 reference statements)

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“…In recent years, circRNAs have been discovered as new regulators of gene expression and have been incriminated in the pathogenesis of various cancers (B. Chen & Huang, ; S. Chen & Zhao, ; J. Chen, Li, Zheng, et al, ). Some circRNAs have been validated as diagnosis, therapeutic, and prognosis biomarkers of diverse tumors (B. Chen & Huang, ; S. Chen, Li, Zhao, Xiao, & Guo, ; Han, Xia, Zhang, Zheng, & Li, ; Jiang et al, ; Kulcheski et al, ; P. Li et al, ; W. Li et al, ; Lu et al, ; Meng et al, ). Here, we established that circ‐U2AF1 might play an oncogene role in glioma.…”

Section: Discussionmentioning

confidence: 99%

Circ‐U2AF1 promotes human glioma via derepressing neuro‐oncological ventral antigen 2 by sponging hsa‐miR‐7‐5p

Min

Cai

et al. 2018

Journal Cellular Physiology

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The prognosis for human glioma, a malignant tumor of the central nervous system, is poor due to its rapid growth, genetic heterogeneity, and inadequate understanding of its underlying molecular mechanisms. Circular RNAs composed of exonic sequences, represent an understudied form of noncoding RNAs (ncRNAs) that was discovered more than a decade ago, function as microRNA sponges. We aimed to assess the relationship between circ‐U2AF1 (CircRNA ID: hsa_circ_0061868) and hsa‐mir‐7‐5p and examine their effects on proliferation, apoptosis, and the metastatic phenotype of glioma cells regulated by neuro‐oncological ventral antigen 2 (NOVA2). We found that the expression levels of circ‐U2AF1 and NOVA2 were upregulated, while hsa‐miR‐7‐5p was downregulated in human glioma tissues and glioma cell lines. Our data and bioinformatic analysis indicated the association of these molecules with glioma grade, a positive correlation between circ‐U2AF1 and NOVA2 expression levels and a negative correlation of hsa‐miR‐7‐5p with both circ‐U2AF1 and NOVA2, respectively. In addition, silencing of circ‐U2AF1 expression resulted in increased hsa‐miR‐7‐5p expression and decreased NOVA2 expression both in vitro and in vivo. Luciferase assay confirmed hsa‐miR‐7‐5p as a direct target of circ‐U2AF1 and NOVA2 as a direct target of hsa‐miR‐7‐5p. Functionally, silencing of circ‐U2AF1 inhibits glioma development by repressing NOVA2 via upregulating hsa‐miR‐7‐5p both in vitro and in vivo. Thus, we assumed that circ‐U2AF1 promotes glioma malignancy via derepressing NOVA2 by sponging hsa‐miR‐7‐5p. Taken together, we suggest that circ‐U2AF1 can be a prognostic biomarker and the circ‐U2AF1/hsa‐miR‐7‐5p/NOVA2 regulatory pathway may be a novel therapeutic target for treating gliomas.

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Section: Discussionmentioning

confidence: 99%

Circ‐U2AF1 promotes human glioma via derepressing neuro‐oncological ventral antigen 2 by sponging hsa‐miR‐7‐5p

Min

Cai

et al. 2018

Journal Cellular Physiology

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“…circRNAs will be more sensitive and specific as cancer biomarkers for diagnosis and therapy than antigen–antibody reactions. Thus, hsa_circ_101280 can be used as an HCC biomarker and can be detected by qRT‐PCR and in situ hybridization . In addition, several circRNAs have been confirmed to act as miRNA sponges and to be involved in circRNA‐miRNA‐mRNA axis .…”

Section: Discussionmentioning

confidence: 99%

“…Thus, hsa_circ_101280 can be used as an HCC biomarker and can be detected by qRT-PCR and in situ hybridization. 35,36 In addition, several circRNAs have been confirmed to act as miRNA sponges and to be involved in circRNA-miRNA-mRNA axis. 37 For instance, circ-SRY functioned as a sponge of miR-138 in colorectal and ovarian cancers.…”

Section: Discussionmentioning

confidence: 99%

Hsa_circ_101280 promotes hepatocellular carcinoma by regulating miR‐375/JAK2

Cao

Wang

et al. 2018

Immunol Cell Biol

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In this study, we sought to predict the effects of a certain circular RNA (circRNA), hsa_circ_101280 (also known as hsa_circ_0100929 and hsa_circ_SLAIN1), on hepatocellular carcinoma (HCC) cells and to determine the potential mechanism. After screening differentially expressed circRNAs in HCC tissues through Gene Expression Omnibus data analysis, hsa_circ_101280 was found to be highly expressed, and its high expression was verified in HCC cell lines with qRT‐PCR along with the low expression of its downstream miRNA miR‐375. Colony formation and flow cytometry assays showed that both hsa_circ_101280 silencing and miR‐375 overexpression restrained proliferation and promoted apoptosis in HCC cells. JAK2 was identified as a downstream mRNA target of miR‐375 by RNA pull‐down and dual‐luciferase reporter gene assays, its expression in HCC cell lines were positively regulated by hsa_circ_101280 and negatively by miR‐375 expression. Furthermore, the silencing of hsa_circ_101280 significantly inhibited the growth of HCC xenografts in nude mice, with the downregulated expression of JAK2. Overall, both the in vitro and in vivo studies revealed that hsa_circ_101280 largely facilitated the tumorigenesis of HCC, characterized by the promoted proliferation and suppressed apoptosis of HCC cells, by sponging miR‐375 and upregulating JAK2.

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“…As previously reported, circRNAs are enriched and stable in exosomes [51, 52], which indicates that it might be possible to diagnose cancer by detecting plasma or serum circRNAs. It is believed that circRNAs could be useful as a noninvasive tumor screening tool for clinical practice in the future [53]. More large-scale studies are needed to evaluate the diagnostic accuracy of plasma or serum circRNAs for digestive system malignancies.…”

Section: Discussionmentioning

confidence: 99%

A Meta-Analysis of the Diagnostic Accuracy of Circular RNAs in Digestive System Malignancy

Chen¹,

Zhang²,

Han³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Circular RNAs (circRNAs), a novel class of noncoding RNAs, have been found to be dysregulated in various cancers. However, the clinical application value of these circRNAs in digestive system cancers remains to be clarified. We aimed to comprehensively explore the potential role of circRNAs as diagnostic indicators in digestive system malignancies. Methods: Relevant studies were systematically retrieved from PubMed, Web of Science and the Cochrane Library. The data that were required to complete 2 × 2 contingency tables were obtained from the included studies. Stratified analyses by cancer type, sample size and publication year were performed. Results: Thirteen studies with 2,276 individuals were included in the meta-analysis. The pooled sensitivity and specificity of circRNAs in the diagnosis of digestive system malignancy were 0.72 [95% confidence interval (CI): 0.65-0.77] and 0.77 (95% CI: 0.72-0.81), respectively. The overall positive likelihood ratio was 3.09 (95% CI: 2.64-3.62), and the overall negative likelihood ratio was 0.37 (95% CI: 0.31-0.44). The pooled diagnostic odds ratio was 8.38 (95% CI: 6.86-10.25), and the overall area under the curve was 0.81 (95% CI: 0.77-0.84), indicating good discriminative ability of circRNAs as biomarkers for digestive system malignancy. Conclusion: circRNAs distinguish patients with digestive system cancer from controls with relatively high diagnostic accuracy. circRNAs may be used as potential biomarkers for the diagnosis of digestive system malignancy.

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Circular RNAs: A novel type of biomarker and genetic tools in cancer

Cited by 92 publications

References 100 publications

Circ‐U2AF1 promotes human glioma via derepressing neuro‐oncological ventral antigen 2 by sponging hsa‐miR‐7‐5p

Circ‐U2AF1 promotes human glioma via derepressing neuro‐oncological ventral antigen 2 by sponging hsa‐miR‐7‐5p

Hsa_circ_101280 promotes hepatocellular carcinoma by regulating miR‐375/JAK2

A Meta-Analysis of the Diagnostic Accuracy of Circular RNAs in Digestive System Malignancy

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