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Effect of cedarol on proliferation,migration and invasion of breast cancer cells by regulating miR-503-5p/TCF3 axis
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DOI   10.11656/j.issn.1672-1519.2023.09.16
Key Words   cedarol;miR-503-5p/TCF3 axis;breast cancer;proliferation;migration;cell invasion
Author NameAffiliation
FENG Yanzhi Department of Breast Surgery, People's Hospital of Zhengzhou, Zhengzhou 450099, China 
NIU Bing Department of Breast Surgery, People's Hospital of Zhengzhou, Zhengzhou 450099, China 
YE Beibei Department of Breast Surgery, People's Hospital of Zhengzhou, Zhengzhou 450099, China 
Abstract
    [Objective] To investigate the effect of cedarol on the proliferation,migration and invasion of breast cancer(BC) cells by regulating miR-503-5p/T cell factor 3(TCF3) axis. [Methods] The expression levels of miR-503-5p and TCF3 protein in BC tissues and cells were detected by real-time fluorescent quantitative PCR(qRT-PCR) and Western blot respectively;MCF7 cells were treated with different concentrations of cedarol(0,14,28,56,112,225 μmol/L). Cell proliferation was detected by MTT method;MCF7 cells were grouped into control group(normal culture),cedarol group(112 μmol/L),inhibitor-NC(transfected with inhibitor-NC),miR-503-5p inhibitor group(transfected with miR-503-5p inhibitor). The expression level of miR-503-5p in cells was detected by qRT-PCR;cell proliferation,migration and invasion were detected by MTT method,Edu staining and Transwell cell,respectively;Western blot was applied to detect the expression of proliferating cell nuclear antigen(PCNA),matrix metalloproteinase-2(MMP-2) and TCF3 proteins;the target relationship between miR-503-5p and TCF3 was verified by double luciferase reporter gene experiment;the effect of cedarol on the growth of BC tumor and the miR-503-5p/TCF3 axis was verified by the tumor formation experiment in mice. [Results] In BC tissues and cells,the expression level of miR-503-5p decreased and the expression level of TCF3 protein increased(P<0.05). Cedarol inhibited the proliferation,migration and invasion of MCF7 cells and decreased the expression of PCNA,MMP-2 and TCF3 proteins in MCF7 cells(P<0.05),inhibition of miR-503-5p expression could reverse the inhibitory effects of cedarol on the proliferation,migration and invasion of MCF7 cells(P<0.05);the double luciferase reporter gene experiment confirmed that miR-503-5p targeted the expression of MCF7(P<0.05);the results of tumor-bearing experiment in mice showed that cedarol could reduce the weight and volume of transplanted tumors,increase the level of miR-503-5p in transplanted tumor,and reduce the level of TCF3 and MMP-2 expression(P<0.05). [Conclusion] Cedarol can inhibit the proliferation,migration and invasion of BC cells,and its mechanism may be related to the regulation of miR-503-5p/TCF3 axis,which may become a new target for the treatment of BC.

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