Breast Cancer

CircMMP11[Circular RNA]

miR-625-5p[miRNA]

ZEB2[mRNA]

breast cancer cells

Homo sapiens (human)

Cancer Cell Int. 2021 Feb 25;21(1):133. doi: 10.1186/s12935-021-01816-z.

CircMMP11 regulates proliferation, migration, invasion, and apoptosis of breast cancer cells through miR-625-5p/ZEB2 axis.

Flow cytometry assay;qPCR;RT-qPCR;Western blot;Flow Cytometry assay;Luciferase report assay;RNA pull-down;

BACKGROUND: Circular RNAs (circRNAs) have been demonstrated to play significant roles in regulating gene expression in tumorigenesis, including breast cancer (BC). This study was designed to explore the role and underlying molecular mechanisms of circMMP11 in BC. METHODS: The real-time quantitative polymerase chain reaction (RT-qPCR) assay was used for examining expression of circMMP11, microRNA-625-5p (miR-625-5p), and Zinc finger E-box binding homeobox-2 (ZEB2). The protein expression of ZEB2, Vimentin, and E-cadherin was assessed by western blot assay. The proliferation ability of BC cells was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazol-3-ium bromide (MTT) and colony-forming assays. The transwell assay was used to measure migration and invasion of BC cells. The apoptotic cells were examined by flow cytometry assay. The interaction association among circMMP11, miR-625-5p, and ZEB2 was confirmed by RNA pull-down and dual-luciferase report assays. A xenograft experiment was established to clarify the role of circMMP11 silencing in vivo. RESULTS: We found that circMMP11 and ZEB2 were overexpressed in BC tissues and cells compared with controls. The suppression of circMMP11 or ZEB2 repressed proliferation, migration, and invasion while induced apoptosis of BC cells. Additionally, miR-625-5p, interacted with ZEB2, was a target of circMMP11 in BC cells. CircMMP11 regulated the expression of ZEB2 by targeting miR-625-5p. Knockdown of circMMP11-mediated effects on BC cells could be abolished by overexpression of ZEB2. Consistently, silencing of circMMP11 impeded the tumor growth in vivo. CONCLUSIONS: CircMMP11/miR-625-5p/ZEB2 axis affected proliferation, migration, invasion, and apoptosis of BC cells through the mechanism of competing endogenous RNAs (ceRNA), indicating that circMMP11 was an oncogenic circRNA in BC.