circCPA4 acts as a prognostic factor and regulates the proliferation and metastasis of glioma

Peng, Hao; Qin, Chaoying; Zhang, Chao; Su, Jun; Xiao, Qian; Xiao, Yao; Xiao, Kai; Liu, Qing

doi:10.1111/jcmm.14541

Cited by 43 publications

(51 citation statements)

References 28 publications

(46 reference statements)

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“…Therefore, cir-cRNAs are important factors in the progression of glioma. CircRNA carboxypeptidase A4 (circCPA4) is a novel identified circRNA, and Hao's team found circCPA4 was positively associated with poor outcome of glioma, and induced glioma cell proliferation and metastasis to promote tumor progression by let-7/CPA4 axis [16], indicating the prognostic and therapeutic potency for glioma. However, large-scale identifications of circCPA4 function in glioma cells were not yet reported.…”

Section: Introductionmentioning

confidence: 99%

CircCPA4 Promotes the Malignant Phenotypes in Glioma via miR-760/MEF2D Axis

et al. 2020

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Circular RNA carboxypeptidase A4 (circCPA4) has been shown to involve in the tumorigenesis of glioma. However, the function and the molecular mechanism of circCPA4 in glioma remain inadequate. Levels of circCPA4 and microRNA (miR)-760 were detected by quantitative real-time polymerase chain reaction. Cell proliferation, apoptosis, migration, and invasion were analyzed using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), colony formation, flow cytometry, and transwell assays, respectively. Western blot was used to detect the protein levels of matrix metallopeptidase 2 (MMP2), MMP9 and myocyte enhancer factor 2D (MEF2D). The interaction between miR-760 and circCPA4 or MEF2D was analyzed by the dual-luciferase reporter assay or RNA pull-down assay. In vivo experiments were conducted using murine xenograft models. We found circCPA4 was highly expressed in glioma, and circCPA4 knockdown suppressed tumor cell proliferative, migratory and invasive behaviors, but enhanced cell apoptosis and radiosensitivity in glioma. CircCPA4 directly bound to miR-760 to suppress its expression, and miR-760 inhibition reversed circCPA4 knockdown-mediated inhibition of cell malignant phenotypes in glioma. MEF2D was a target of miR-760, and miR-760 performed anti-tumor effects by targeting MEF2D in glioma cells. Meanwhile, we found circCPA4 could indirectly regulate MEF2D by sponging miR-760. Importantly, xenograft analysis suggested that circCPA4 knockdown impeded tumor growth in vivo via regulating miR-760 and MEF2D. In conclusion, circCPA4 knockdown suppressed cell malignant phenotypes in glioma via miR-760/MEF2D axis to impede the progression of glioma, suggesting potential therapeutic targets for glioma treatment.

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Section: Introductionmentioning

confidence: 99%

CircCPA4 Promotes the Malignant Phenotypes in Glioma via miR-760/MEF2D Axis

et al. 2020

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“…circ-0012129 also was reported to significantly increased in glioma tissues, and its knockdown significantly suppressed the proliferation and invasion abilities of U373 and SHG44 gliomas lines through upregulating the expression of miR-661 [86]. circCPA4, circSCAF11, circ-PITX1 were significantly up-regulated in GBM, accelerated the glioma tumorigenesis via let7/CPA4, miR421/SP1/VEGFA, miR-379-5p/MAP3K2 axis, respectively [87][88][89], while Cir-cMTO1 markedly down-regulated and inhibited GBM proliferation through miR92/WWOX pathway [90]. Additionally, circPTN promoted glioma growth and stemness through sponging miR-145-5p and miR-330-5p, subsequently increased Nestin, CD133, SOX9, and SOX2 expression [91].…”

Section: Circrnas Act As Microrna Sponges On the Proliferation And Inmentioning

confidence: 94%

“…To date, the association between circRNA expression in tissues or peptides/proteins encoding by circRNA and clinical parameters have been largely reported. Circ_ 0034642, circ_0074362, cir-ITCH, circHIPK3 and cir-cCPA4 linked to clinical severity and poor prognosis in patients with glioma [50,53,87,113,114]. Wang et al proposed that the reduction of circ_0001649 was linked to larger tumor size and advanced WHO grade, indicating circ_0001649 may be an independent prognostic marker after surgery.…”

Section: Circrnas Are Potential Novel Biomarkers For Diagnosis and Prmentioning

confidence: 99%

Functions and clinical significance of circular RNAs in glioma

et al. 2020

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CircRNAs are a class of single-stranded RNA molecules with a covalently closed loop structure and have been characterized by high stability, abundance, conservation, and display tissue/developmental stage-specific expression, furthermore, based on the abundance in distinct body fluids or exosomes, circRNAs present novel biomarkers and targets for the diagnosis and prognosis of cancers. Recently, the regulatory mechanisms of biogenesis and molecular functions, including miRNAs and RBPs sponge, translation as well as transcriptional and splicing regulation, have been gradually uncovered, although various aspects remained to be elucidated in combination with deep-sequence and bioinformatics. Accumulating studies have indicated that circRNAs are more enriched in neuronal tissues partly due to the abundance of specific genes promoting circularization, suggesting dysregulation of circRNAs is closely related to diseases of the nervous system, including glioma. In this review, we elaborate on the biogenesis, functions, databases as well as novel advances especially involved in the molecular pathways, highlight its great value as diagnostic or therapeutic targets in glioma.

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“…For example, circRNA CPA4 acts as a prognostic factor and regulates glioma growth and metastasis. 23 Overexpressed circRNA UBE2D2 facilitates breast cancer progression and predicts dreadful BC patient prognosis. 24 In AAA, circRNAs expression profiling indicated the potential participation of circRNAs in AAA.…”

Section: Discussionmentioning

confidence: 99%

Circular RNA CCDC66 facilitates abdominal aortic aneurysm through the overexpression of CCDC66

Yang

Wang

Meng

et al. 2020

Cell Biochemistry & Function

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Funding information The fifth group of bosom friends and talents plan of Hanyang District, Wuhan Abdominal aortic aneurysm (AAA) is fatal meanwhile unpredictable asymptomatic cardiovascular disease. Available data suggests the potential participation of circular RNAs (circRNAs) in AAA pathogenesis. But direct evidence is limited. The present study is to functionally and mechanically characterize circRNA CCDC66 (circCCDC66) in AAA. Previous work indicated the differentially expressed circCCDC66 in AAA. At molecular level, circCCDC66, miR-342-3p and CCDC66 transcript were measured through real-time quantitative polymerase chain reaction assay. Functionally, we examined the cellular behaviours of circCCDC66-depleted or CCDC66-depleted vascular smooth muscle cells (VSMCs) including proliferation and apoptosis. It elucidated that depletion of circCCDC66 induced proliferation facilitation and apoptosis reduction. Mechanically, we addressed the interplay among circCCDC66, miR-342-3p and CCDC66 transcript using RNA immunoprecipitation, RNA pull-down and luciferase reporter experiments. Through mechanical validation, we discovered the positive regulation of circCCDC66 on its host gene CCDC66. Loss of CCDC66 mimicked the effects of circCCDC66 silencing on VSMC growth. Moreover, it uncovered that circCCDC66 regulated CCDC66-dependent VSMC growth through sponging miR-342-3p. Rescue experiments aimed to address the functional role of regulatory network formed by circCCDC66, miR-342-3p and CCDC66 in VSMC growth and apoptosis. Suppressing miR-342-3p or overexpressing CCDC66 could reverse VSMC growth caused by circCCDC66 deficiency. Our study further emphasized and first unveiled the function of circCCDC66 in VSMC proliferation. CircCCDC66 upregulated its host gene through its role of miR-342-3p sponge, and hinted a novel molecular mechanism in AAA. Significance of the study: It was firstly displayed in our study that depletion of circCCDC66 induced proliferation augmentation and apoptosis reduction of vascular smooth muscle cells (VSMCs). Meanwhile, circCCDC66/miR-342-3p/CCDC66 axis was proved can play the function of modulating the cell proliferation and apoptosis of VSMCs, which provided us a novel molecular mechanism in AAA.

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circCPA4 acts as a prognostic factor and regulates the proliferation and metastasis of glioma

Cited by 43 publications

References 28 publications

CircCPA4 Promotes the Malignant Phenotypes in Glioma via miR-760/MEF2D Axis

CircCPA4 Promotes the Malignant Phenotypes in Glioma via miR-760/MEF2D Axis

Functions and clinical significance of circular RNAs in glioma

Circular RNA CCDC66 facilitates abdominal aortic aneurysm through the overexpression of CCDC66

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