Circular RNA circ-ZEB1 acts as an oncogene in triple negative breast cancer via sponging miR-448. (September 2020)

• Record Type: Journal Article
• Authors: Pei, Xinhong; Zhang, Yujie; Wang, Xinxing; Xue, Bingjian; Sun, Meng; Li, Huixiang
• Is Part Of: International journal of biochemistry & cell biology. Volume 126(2020)
• Publication Date: 2020-09
• Subjects: Triple negative breast cancer -- circRNA -- ceRNA -- miR-448 -- eEF2K; Biochemistry -- Periodicals; Cytology -- Periodicals; Biochemistry -- Periodicals; Cell Biology -- Periodicals; Biochimie -- Périodiques; Cytologie -- Périodiques; Biochimie; Cytologie; Biochemistry; Cytology; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); Periodicals; 572.05
• DOI: 10.1016/j.biocel.2020.105798
• Languages: English
• ISSNs: 1357-2725

Abstract

Abstract: Background: Circular RNAs (circRNAs) play an important role in tumor development. The miRNA sponge is a common role played by circRNAs in various tumors, including breast cancer. Objective: This study aimed to explore the role of circ-ZEB1 in the proliferation and apoptosis of triple negative breast cancer (TNBC) cells. Methods: The expressions of several circRNAs which were predicted to be bound with miR-448 were detected in 30 clinical TNBC tumor tissues and paired paracancer tissues. The cell counting kit-8 assay was performed to detect the TNBC cell proliferation. The TNBC cell apoptosis was detected using the TUNEL assay. The binding between circ-ZEB1 and miR-448, as well as between miR-448 and eukaryotic elongation factor 2 kinase (eEF2 K), was detected using the RNA pull-down assay and/or the luciferase reporter assay. The effect of circ-ZEB1 knockdown on TNBC tumor growth was detected using the mouse xenograft model. Results: Compared with normal tissues and breast epithelial cells, the expression of circ-ZEB1 was markedly higher in TNBC tumor tissues and tumor cell lines. The small hairpin RNA-mediated circ-ZEB1 knockdown inhibited TNBC cell proliferation and induced cell apoptosis. The RNA pull-down assay and the luciferase reporter assay confirmed the binding between circ-ZEB1 and miR-448, as well as between miR-448 and eEF2 K. The knockdown of circ-ZEB1 was proven to inhibit TNBC cell proliferation and tumor growth via releasing miR-448, and subsequently reducing the expression of the miR-448 target, eEF2 K. Conclusion: In conclusion, our findings identified a new functional circ-ZEB1 in TNBC tumorigenesis, and revealed the important regulatory role of circ-ZEB1 via sponging miR-448, providing a novel insight for TNBC pathogenesis.