Dataset Information

Circular RNA hsa_circ_0131242 Promotes Triple-Negative Breast Cancer Progression by Sponging hsa-miR-2682.

ABSTRACT: Objective:CircRNAs are emerging as vital regulators in a variety of cancers. However, the expression pattern and potential mechanism of circRNAs in triple-negative breast cancer remain unclear. In this study, we aim to systematically investigate circRNAs alteration in triple-negative breast cancer tissues. Methods:Microarray and bioinformatics analyses were used to identify circRNAs expression in cancer tissues. qRT-PCR was conducted to measure the expression of RNAs. Cell Counting Kit-8, wound-healing and transwell assays were conducted to investigate the function of circRNAs. Dual-luciferase reporter assay was performed to validate target binding. Results:Hsa_circ_0131242 was highly expressed in both cancer tissues and cell lines compared to control. Subsequently, statistical analyses revealed that high expression of hsa_circ_0131242 was positively correlated with advanced tumor stages and poorer clinical features in cancer patients. Hsa_circ_0131242 knockdown could suppress the progression of breast cancer cells. Bioinformatics prediction and luciferase reporter assay showed that hsa_circ_0131242 acted as a sponge for hsa-miR-2682. Moreover, co-transfection of hsa-miR-2682 inhibitor and si-hsa_circ_0131242 rescued cell proliferation and migration in BT549 and MDA-MB-468 cell lines. Conclusion:Our study identified hsa_circ_0131242 expression in TNBC for the first time and found that hsa_circ_0131242 may promote triple-negative breast cancer progression by sponging hsa-miR-2682.

SUBMITTER: Li Y

PROVIDER: S-EPMC7261810 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Circular RNA hsa_circ_0131242 Promotes Triple-Negative Breast Cancer Progression by Sponging hsa-miR-2682.

Li Yueting Y Shi Pengxu P Zheng Tianzhi T Ying Ziwei Z Jiang Daqing D

OncoTargets and therapy 20200527

<h4>Objective</h4>CircRNAs are emerging as vital regulators in a variety of cancers. However, the expression pattern and potential mechanism of circRNAs in triple-negative breast cancer remain unclear. In this study, we aim to systematically investigate circRNAs alteration in triple-negative breast cancer tissues.<h4>Methods</h4>Microarray and bioinformatics analyses were used to identify circRNAs expression in cancer tissues. qRT-PCR was conducted to measure the expression of RNAs. Cell Countin ...[more]

PMID: 32547106

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Project description:BackgroundFetal growth restriction (FGR) is a worldwide problem, and a major cause of perinatal morbidity. The precise molecular mechanisms involved in placental development and function during FGR remain poorly understood. Circular RNAs (circRNAs) are important biological molecules associated with disease pathogenesis. However, the role of circRNAs in FGR has not been well studied.MethodscircRNA expression profiles in placental tissues with and without FGR were identified by circRNA microarray. circRNA expression was verified by quantitative reverse-transcription PCR (RT-qPCR) assay. The effect of hsa_circ_0000848 and hsa-miR-6768-5p on HTR-8 cell apoptosis, migration, and invasion was evaluated. The association between hsa_circ_0000848 and hsa-miR-6768-5p was confirmed by dual luciferase activity and anti-AGO2 RNA immunoprecipitation (RIP) assays. Protein levels were examined via western blotting.ResultsRT-qPCR results showed that hsa_circ_0000848 expression was significantly down-regulated in FGR placenta. Hsa_circ_0000848 overexpression and hsa-miR-6768-5p inhibitor suppressed apoptosis, and promoted cell migration and invasion. In addition, hsa_circ_0000848 overexpression and hsa-miR-6768-5p inhibitor increased the protein abundance of BCL2, MMP2 and MMP9, and decreased the protein abundance of cleaved caspase-3, cleaved caspase-9, and BAX, whereas hsa_circ_0000848 knockdown caused the opposite effect. Moreover, a significant increase in hsa-miR-6768-5p expression and a negative correlation between hsa_circ_0000848 and hsa-miR-6768-5p were identified in the FGR tissues. Luciferase reporter and RIP assay results revealed binding of hsa-miR-6768-5p to hsa_circ_0000848. Furthermore, hsa-miR-6768-5p overexpression eliminated the effect of hsa_circ_0000848 overexpression in HTR-8 cells.Conclusionshsa_circ_0000848 expression is significantly down-regulated in the FGR placenta. hsa_circ_0000848 promotes trophoblast cell migration and invasion, and inhibits cell apoptosis via the sponging of hsa-miR-6768-5p. Our study provided a novel insight into mechanisms underlying the pathogenesis of FGR, as well as into new strategies for the treatment of FGR.

Project description:As a recently discovered noncoding RNA, circular RNAs (circRNAs) have been identified to play key roles in cancer biology; however, the detailed functions and mechanisms of circRNAs in hepatocellular carcinoma (HCC) remain largely unclarified. RNA-seq analysis was used to screen the expression profiles of circRNAs in HCC. CircZNF566 expression in HCC tissues and cell lines was detected by qRT-PCR. In vitro CCK-8, colony formation, wound healing, transwell migration, and invasion assays and in vivo tumorigenesis and metastasis assays were conducted to determine the functions of circZNF566. Luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays were also performed to confirm the relationship between circZNF566 and miR-4738-3p. Bioinformatics analysis and luciferase reporter assays were employed to determine whether miR-4738-3p regulates tryptophan 2,3-dioxygenase (TDO2) expression. Finally, immunohistochemistry (IHC) was used to detect the level of TDO2 and determine its prognostic value. CircZNF566 was significantly upregulated in HCC tissues and cell lines. High circZNF566 expression in HCC tissues was positively correlated with clinicopathological features and poor prognosis. Functionally, in vitro experiments showed that circZNF566 promoted HCC cell migration, invasion, and proliferation, whereas in vivo experiments showed that circZNF566 promoted tumorigenesis and metastasis. Mechanistically, circZNF566 acted as a miR-4738-3p sponge to relieve the repressive effect of miR-4738-3p on its target TDO2. In addition, miR-4738-3p suppressed HCC cell migration, invasion, and proliferation, while TDO2 was positively correlated with pathological features and poor prognosis and promoted cell migration, invasion, and proliferation in HCC. CircZNF566 is a novel tumor promoter in HCC and functions through the circZNF566/ miR-4738-3p /TDO2 axis; in addition, circZNF566 may serve as a novel diagnostic marker, prognostic indicator, and target for the treatment of HCC.

Dataset Information

Circular RNA hsa_circ_0131242 Promotes Triple-Negative Breast Cancer Progression by Sponging hsa-miR-2682.

Publications

Circular RNA hsa_circ_0131242 Promotes Triple-Negative Breast Cancer Progression by Sponging hsa-miR-2682.

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