Increased Fucosylation Has A Pivotal Role In Multidrug Resistance Of Breast Cancer Cells Through MiR-224-3p Targeting FUT4

Objective: To explore the differential expression of fucosyltransferase(FUT)genes in human breast cancer cell lines and its drug-resistant cell lines,and to clarify the mechanism of based on miR-224-3p probe to regulate fucosylation in breast cancer multidrug resistance.This study might provide new tactics and target for breast cancer multidrug resistance diagnosis,prediction and treatment.Methods:(1)N-glycan composition was detected in drug-resistant T47D/ADR cells and parental T47 D cells using a mass spectrometer.(2)The differential expression of FUT genes was compared in breast cancer cell lines and its drug-resistant cell lines by using real-time PCR.(3)To detect the chemosensitivity to anti-tumor drugs of T47D/ADR and T47 D in vitro and in vivo,FUT expression was down-regulated in T47D/ADR cells,and FUT expression was up-regulated in T47 D cells.(4)Using dual luciferase experiments,we verify the relationship of miR-224-3p and FUT4.Manipulating the differentially expressed miR-224-3p,the expression of FUT4 and the chemosensitivity to anti-tumor drugs of T47D/ADR and T47 D were analyzed both in vitro and in vivo.Results:(1)The N-glycan compositions of the cell membrane were different in T47D/ADR and T47 D cell lines.(2)Differential expression of FUT4 was most significant in human breast cancer cell line and its drug-resistant cell line expression.(3)Silencing of FUT4 in T47D/ADR cells could increase the chemosensitivity to anti-tumor drugs;overexpressing of FUT4 in T47 D cells could decrease the chemosensitivity to anti-tumor drugs.(4)Silencing of miR-224-3p in T47 D cells resulted in increased expression of FUT4;overexpressing of miR-224-3p in T47D/ADR cells could decrease the expression of FUT4,and increase the chemosensitivity to anti-tumor drugs.Conclusion:(1)The expression of FUT4 in human breast cancer cells T47 D and its drug-resistant cells T47D/ADR was significant difference.The difference is associated with multidrug resistance in breast cancer.(1)The expression of miR-224-3p in human breast cancer cells T47 D and its drug-resistant cells T47D/ADR was significant difference.The difference is associated with multidrug resistance in breast cancer.(2)MiR-224-3p could reverse multidrug resistance in breast cancer cells by targeting the FUT4 expression.