MUC1 Mediates Iron Metabolism Disorder in Triple-Negative Breast Cancer Cells and Quercetin Intervention
In order to study the effect of human mucin 1(MUC1)on the iron homeostasis in triple-negative breast cancer(TNBC)and investigate the new mechanism of quercetin against the TNBC proliferation,the expres-sion of MUC1 in the normal breast tissue and breast cancer tissue along with its correlation with prognosis were ana-lyzed by the bioinformatics method in this study.The MUC1 overexpression cell model was constructed using lenti-virus transfection,and the triple-negative breast cancer MDA-MB-468 cells were divided into a control group,a quercetin group with different concentrations,and a GO203(MUC1 inhibitor)group.The cell viability was detected by the CCK-8 method,the level of free Fe2+was detected by a fluorescence probe of ferrous ion,the ex-pression of MUC1 gene was detected by qPCR,and the expression of MUC1 and iron metabolism-related proteins was detected by Western Blot.The results showed that the expression of MUC1 in the breast cancer tissue was much higher than that in the normal breast tissue(P<0.05),and the prognosis of TNBC patients was closely related to the high expression of MUC1(P<0.01).Compared with the control group,the proliferation of MUC1 over-expression mod-el cells was significantly accelerated(P<0.01),accompanied by an increase in the intracellular Fe2+level(P<0.01)and also increases in the expressions of ferric input protein TFR1 and FTH1(P<0.05,P<0.05).However,there were no significant changes in the expressions of iron exporting protein SLC40A1,ferritinophagy regulatory factor NCOA4 and upstream regulatory factor NRF2(P>0.05).Quercetin could reduce the MUC1 gene and protein ex-pressions(P<0.01,P<0.05);quercetin and G0203(MUC1 inhibitors)could inhibit the TNBC cell proliferation(P<0.05),reduce the iron content in cells(P<0.01),lower the iron input TFR1 protein and FTH1 expressions(P<0.01,P<0.05),and increase the expression of iron exporting protein SLC40A1(P<0.05).In conclusion,the high expression of MUC1 can affect the expression of iron metabolism-related proteins,leading to an iron homeosta-sis imbalance,and then the iron accumulation promotes the cell proliferation.Quercetin can significantly inhibit the proliferation of MDA-MB-468 cells,which may regulate the iron homeostasis by down-regulating MUC1 and then reduce the intracellular iron levels.
quercetintriple-negative breast cancerMUC1iron homeostasisanti-tumor
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