Oxymatrine inhibits proliferation and migration of breast cancer cells by inhibiting miRNA-188 and upregulating its target gene, PTEN

Xiaoying Ma,Qinghua Zhang,Zijiang Sang,Wenbiao Ma

doi:10.4314/tjpr.v20i11.5

Xiaoying Ma, Qinghua Zhang + Show 2 more

Open Access

https://doi.org/10.4314/tjpr.v20i11.5

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Abstract

Purpose: To explore the potential biological functions of oxymatrine on breast cancer (BCa) cells and the underlying molecular mechanism.Methods: Relative levels of microRNA-188 (miRNA-188) and PTEN (gene of phosphate and tension homology deleted on chromosome ten) in BCa cells, MDA-MB-231 and TB549, were determined. The influence of oxymatrine treatment, miRNA-188 and PTEN on proliferative and migratory abilities in BCa cells were assessed by 3-(4,5-imethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), cell counting kit-8 (CCK-8) and Transwell assay, respectively. The binding relationship between miRNA-188 and PTEN was evaluated by dual-luciferase reporter gene assay.Results: Oxymatrine downregulated miRNA-188 and upregulated PTEN in BCa cells. Proliferative and migratory activities in BCa were inhibited by treatment of oxymatrine (p < 0.05). Dual-luciferase reporter gene assay results indicated that PTEN was the target gene of miRNA-188. Furthermore, rescue experiments demonstrated that the regulatory loop, oxymatrine/miRNA-188/PTEN, was involved in the regulation of the migration and proliferation of BCa.Conclusion: Oxymatrine treatment inhibits BCa progression by downregulating miRNA-188, leading to the upregulation of PTEN. The results of the current study may provide new insight into the diagnosis and treatment of BCa.

Highlights

Breast cancer (BCa) is the second leading malignancy globally, and about one-eighth of females suffer from breast cancer (BCa) [1]
BCa cells were treated with 50 μM Oxymatrine for 24, 48 or 72 h, respectively
Results from cell counting kit-8 (CCK-8) assay revealed the declined viability in BCa cells treated with Oxymatrine compared to those of control (Figure 1 B and C)

Summary

Introduction

Breast cancer (BCa) is the second leading malignancy globally, and about one-eighth of females suffer from BCa [1]. A therapeutic strategy for metastatic breast cancer (MBC) is limited. It is necessary to clarify mechanisms underlying the tumorigenesis and tumor progression of BCa, improving diagnostic accuracy and prognosis of BCa patients. In BCa, dysregulated miRNAs are able to affect tumor cell behavior, thereby mediating tumor progression [7]. A previous study demonstrated that miRNAs serve as biological markers and therapeutic tools for BCa [8]. Determination of miRNA levels helps to classify subtypes of BCa and evaluate therapeutic outcomes [9]. MicroRNAs can be utilized as non-invasive tool for effectively monitoring disease progression in BCa [9,10]

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Conclusion