Circular RNAs in Human Cancer

Wang, Xiong; Li, Huijun; Lu, Yanjun; Cheng, Liming

doi:10.3389/fonc.2020.577118

Cited by 37 publications

(33 citation statements)

References 189 publications

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“…As a result, circRNA contribute to the development of many diseases. In cancers, not only are the expression levels of circRNA correlated with distinct clinicopathological characteristics and thus established as cancer biomarkers, but increasing molecular mechanisms have been revealed for their biological functions [11,12]. The circRNA ephrin type-B receptor 4 (circEPHB4) is a circRNA derived from the receptor tyrosine kinase EPHB4.…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: CircRNA EPHB4 modulates stem properties and proliferation of gliomas via sponging miR‐637 and up‐regulating SOX10

et al. 2020

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Gliomas are the most common type of primary brain tumors. CircRNA ephrin type-B receptor 4 (circEPHB4) is a circular RNA derived from the receptor tyrosine kinase EPHB4. However, the clinical significance and the specific roles of circEPHB4 in gliomas and glioma cancer stem cells (CSCs) have not been studied. Here, we found that circEPHB4 (hsa_circ_0081519) and SOX10 were up-regulated, while miR-637 was down-regulated in glioma tissues and cell lines. Consistently, circEPHB4 was positively correlated with SOX10, but negatively correlated with miR-637. The altered expressions of these molecules were independently associated with overall survival of patients. CircEPHB4 up-regulated SOX10 and Nestin by directly sponging miR-637, thereby stimulating stemness, proliferation, and glycolysis of glioma cells. Functionally, silencing circEPHB4 or increasing miR-637 levels in glioma cells was sufficient to inhibit xenograft growth in vivo. In conclusion, the circEPHB4/miR-637/SOX10/Nestin axis plays a central role in controlling stem properties, self-renewal as well as glycolysis of glioma cells and predicts the overall survival of glioma patients. Targeting this axis might provide a therapeutic strategy for malignant gliomas.

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Section: Introductionmentioning

confidence: 99%

RETRACTED: CircRNA EPHB4 modulates stem properties and proliferation of gliomas via sponging miR‐637 and up‐regulating SOX10

et al. 2020

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“…Dysregulation of circRNAs has been found in various human diseases including cancers. 25 Increasing evidence has reported the involvement of circRNAs in vital biological processes such as proliferation, metastasis and therapy resistance. 26 Current studies are mainly focused on biology functions of circRNAs, whereas little is known about their clinical diagnostic value in human diseases.…”

Section: Discussionmentioning

confidence: 99%

CircMTO1 inhibits liver fibrosis via regulation of miR‐17‐5p and Smad7

Wang

Dong

Guo

et al. 2019

J Cellular Molecular Medi

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Circular RNAs (circRNAs), often dysregulated in a variety of human diseases, participate in the initiation and development of cancers. Recently, circMTO1 (a circRNA derived from MTO1 gene), identified as a tumor suppressor, has been shown to contribute to the suppression of hepatocellular carcinoma. The present study aimed to explore the clinical significance and roles of circMTO1 in liver fibrosis. Here, we found that serum circMTO1 was significantly down‐regulated in chronic hepatitis B (CHB) patients. Interestingly, serum circMTO1 was negatively correlated with fibrosis stages as well as HAI scores. Receiver operating characteristic curve analysis revealed that serum circMTO1 may serve as a diagnostic biomarker for liver fibrosis in CHB patients. Notably, overexpression of circMTO1 led to the suppression of transforming growth factor‐β1‐induced hepatic stellate cells (HSCs) activation. Bioinformatic analysis and luciferase activity assays indicated that circMTO1 was a target of mircoRNA‐17‐5p (miR‐17‐5p). Data from RNA pull‐down assay further confirmed that circMTO1 interacted with miR‐17‐5p. The inhibitory effects of circMTO1 on HSC activation were suppressed by miR‐17‐5p mimics. Further studies showed that Smad7 was a target of miR‐17‐5p. Moreover, circMTO1‐inhibited HSC activation was also blocked down by loss of Smad7. Taken together, we demonstrate that circMTO1 inhibits liver fibrosis via regulation of miR‐17‐5p and Smad7, and serum circMTO1 may be a novel promising biomarker of liver fibrosis.

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“…It is widely accepted that miRNA function is modulated by circRNA sponging in various pathological and pathophysiological activities [26,27]. Circ_NOTCH3 competes with miR-205-5p to promote the progression of basal-like breast carcinoma [28].…”

Section: Discussionmentioning

confidence: 99%

Circusp34 Promotes Osteosarcoma Proliferation and Invasion by Sponging Mir-16-5p: An in Vivo and in Vitro Analysis

J¹,

Zhang²,

Xu³

et al. 2021

Preprint

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Background Osteosarcoma (OS) is a primary and highly malignant mesenchymal tissue tumor. Although it has achieved a significant breakthrough in therapeutic administration, the specific pathological mechanism remains unclear. CircRNAs are a type of covalently circular RNA with a head-to-tail junction site. Several studies have reported that abnormal expression of circRNAs is closely associated with tumorigenesis and progression. CircRNAs promote or inhibit the progression of OS by sponging miRNAs. In this study, we aimed to investigate the endogenous competition between circRNAs and miRNAs in OS. Methods CircUSP34 expression was detected by qRT-PCR in KHOS and 143B cells. To confirm the effect of circRNAs and miRNAs, function assays including CCK8, EdU, wound healing, transwell, and western blot were performed in OS cells. FISH and dual-luciferase reporter assays were performed to confirm the sponging mechanism of circUSP34 and miR-16-5p. Additionally, qRT-PCR, immunohistochemistry, HE staining, and western blot were used to confirm the expression of proteins and genes in tumor tissues from mice. Results In the present study, we found that circUSP34 promoted OS proliferation, migration, and invasion in vitro and in vivo. circUSP34 and miR-16-5p were upregulated and downregulated, respectively, in OS cells. OS cells’ biological behaviors, such as proliferation, migration, and invasion, were inhibited after circUSP34 knockdown. Western blot results also showed that Vimentin and Ki-67 expression levels were decreased. Similarly, miR-16-5p mimic compromised OS cell proliferation and migration. FISH assay indicated that circUSP34 and miR-16-5p were colocalized in the cytoplasm. The dual-luciferase reporter assay showed that miR-16-5p was sponged by circUSP34. Interestingly, the miR-16-5p mimic partly reversed the inhibitory effect of sh-circUSP34 on the malignancy of OS cells. Finally, animal experiment results about IHC indicated that Vimentin, N-cadherin, and Ki-67 protein expression decreased, but E-cadherin protein expression increased. Conclusion Collectively, circUSP34 promoted OS proliferation, migration, and invasion by sponging miR-16-5p. It can serve as a potential therapeutic target and biomarker.

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Circular RNAs in Human Cancer

Cited by 37 publications

References 189 publications

RETRACTED: CircRNA EPHB4 modulates stem properties and proliferation of gliomas via sponging miR‐637 and up‐regulating SOX10

RETRACTED: CircRNA EPHB4 modulates stem properties and proliferation of gliomas via sponging miR‐637 and up‐regulating SOX10

CircMTO1 inhibits liver fibrosis via regulation of miR‐17‐5p and Smad7

Circusp34 Promotes Osteosarcoma Proliferation and Invasion by Sponging Mir-16-5p: An in Vivo and in Vitro Analysis

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