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Circlular RNA BARD1 (Hsa_circ_0001098) overexpression in breast cancer cells with TCDD treatment could promote cell apoptosis via miR-3942/BARD1 axis.

ABSTRACT: Breast cancer threatened the health of millions of people around the world. Here we explored the influence of TCDD on the expression of circRNA_BARD1 (circ_0001098) in breast cancer and studied the potential molecular mechanism of circRNA_BARD1. The data from GSE76608 was applied to analyze differentially expressed circRNAs and mRNAs. The expressions of circRNA_BARD1, BARD1, miR-3942-3p, miR-4760-3p and apoptosis-related protein p53 were detected by qRT-PCR or western blot. Circinteractome, TargetScan, CIRCNET and dual luciferase reporter assay were employed to uncover the target relationship between circRNA_BARD1/BARD1 and miR-3942-3p/miR-4760-3p. Flow cytometric analysis was used to reveal cell cycle and cell apoptosis. Immunofluorescence was applied to determinate ?-H2AX level. Xenograft assay and in vivo 3-D imaging was implemented to further verify the conclusions in vitro. CircRNA_BARD1 (circ_0001098) was up-regulated in breast cancer with the treatment of TCDD and the up-regulation of circRNA_BARD1 could restrain cell proliferation, block cell cycle and promote cell apoptosis. Moreover, the target relationship between circRNA_BARD1/BARD1 and miR-3942-3p was confirmed. In addition, miR-3942-3p overexpression promoted the disease progression and BARD1 up-regulation inhibited the disease progression in the breast cancer. Similarly, circRNA_BARD1 overexpression induced by TCDD suppressed the growth and metastasis of tumor in vivo. In conclusion, TCDD induced circ_0001098 overexpression and then suppressed breast cancer tumorigenesis via miR-3942-3p/BARD1 axis. The finding of TCDD-circRNA-miRNA-mRNA axis might bring a new perspective for cure strategy of breast cancer.

SUBMITTER: Zhao J

PROVIDER: S-EPMC6343738 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Circlular RNA BARD1 (Hsa_circ_0001098) overexpression in breast cancer cells with TCDD treatment could promote cell apoptosis via miR-3942/BARD1 axis.

Zhao Jianzhu J Zou Huawei H Han Chengbo C Ma Jietao J Zhao Jungang J Tang Jun J

Cell cycle (Georgetown, Tex.) 20181217 24

Breast cancer threatened the health of millions of people around the world. Here we explored the influence of TCDD on the expression of circRNA_BARD1 (circ_0001098) in breast cancer and studied the potential molecular mechanism of circRNA_BARD1. The data from GSE76608 was applied to analyze differentially expressed circRNAs and mRNAs. The expressions of circRNA_BARD1, BARD1, miR-3942-3p, miR-4760-3p and apoptosis-related protein p53 were detected by qRT-PCR or western blot. Circinteractome, Targ ...[more]

PMID: 30521417

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Project description:BackgroundExtracellular vesicles (EVs) derived from tumor cells are implicated in the progression of malignancies through the transfer of molecular cargo microRNAs (miRNAs or miRs). We aimed to explore the role of EVs derived from breast cancer cells carrying miR-182-5p in the occurrence and development of breast cancer.MethodsDifferentially expressed miRNAs and their downstream target genes related to breast cancer were screened through GEO and TCGA databases. miR-182-5p expression was examined in cancer tissues and adjacent normal tissues from patients with breast cancer. EVs were isolated from breast cancer cell line MDA-MB-231 cells and identified. The gain- and loss-of function approaches of miR-182-5p and CKLF-like MARVEL transmembrane domain-containing 7 (CMTM7) were performed in MDA-MB-231 cells and the isolated EVs. Human umbilical vein endothelial cells (HUVECs) were subjected to co-culture with MDA-MB-231 cell-derived EVs and biological behaviors were detected by CCK-8 assay, flow cytometry, immunohistochemical staining, Transwell assay and vessel-like tube formation in vitro. A xenograft mouse model in nude mice was established to observe the tumorigenesis and metastasis of breast cancer cells in vivo.ResultsmiR-182-5p was highly expressed in breast cancer tissues and cells, and this high expression was associated with poor prognosis of breast cancer patients. miR-182-5p overexpression was shown to promote tumor angiogenesis in breast cancer. Moreover, our data indicated that miR-182-5p was highly enriched in EVs from MDA-MD-231 cells and then ultimately enhanced the proliferation, migration, and angiogenesis of HUVECs in vitro and in vivo. Moreover, we found that CMTM7 is a target of miR-182-5p. EVs-miR-182-5p promotes tumorigenesis and metastasis of breast cancer cells by regulating the CMTM7/EGFR/AKT signaling axis.ConclusionsTaken altogether, our findings demonstrates that EVs secreted by breast cancer cells could carry miR-182-5p to aggravate breast cancer through downregulating CMTM7 expression and activating the EGFR/AKT signaling pathway.

Dataset Information

Circlular RNA BARD1 (Hsa_circ_0001098) overexpression in breast cancer cells with TCDD treatment could promote cell apoptosis via miR-3942/BARD1 axis.

Publications

Circlular RNA BARD1 (Hsa_circ_0001098) overexpression in breast cancer cells with TCDD treatment could promote cell apoptosis via miR-3942/BARD1 axis.

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