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 γ-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.