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

Liqiang Qi,Su Lu,Bo Sun,Beibei Yang

doi:10.1186/s12935-021-01816-z

Abstract

BackgroundCircular 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.MethodsThe 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.ResultsWe 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.ConclusionsCircMMP11/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.

Highlights

Breast cancer (BC) is a common female cancer all over the world [1]
CircMMP11 and Zinc finger E-box binding homeobox-2 (ZEB2) were overexpressed in breast cancer (BC) tissues and cells To explore the role of circMMP11 in BC, the expression level of circMMP11 was quantified
The results of real-time quantitative polymerase chain reaction (RT-qPCR) data suggested that circMMP11 were overexpressed in BC tissues and cells when compared with paracancer tissues and MCF-10A cells (Fig. 1a, b)

Summary

Introduction

The morbidity of BC has been rising, over 2 million females were diagnosed with BC according to Circular RNAs (circRNAs), a group of RNA molecules with closed covalent loops, play critical roles in initiation and development of the multiple malignancies [4]. A previous research reported that a series of differentially expressed circRNAs could function as novel biomarkers for BC, including circMMP11 [6]. MiR-625-5p was reported to play significance roles in malignant tumors. The tumor-suppressive function was reported in BC; downregulation of miR-625 was found in BC tissues and cells, which was closely related to poor clinical outcomes of BC patients [10]. 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

Results

Discussion

Conclusion