Effect of circRNA VAPA/miR-377-3p/ZEB2 Axis on Paclitaxel Resistance of Breast Cancer

doi:10.3870/j.issn.1672-8009.2025.06.007

Abstract

Abstract: Objective To investigate the role of circular RNA vesicle-associated membrane protein-associated protein A(circRNA VAPA)on Zinc-finger E-box binding homeobox 2(ZEB2)in paclitaxel resistance of breast cancer by targeting miR-377-3p. Methods Human breast cancer cell line MCF7 and paclitaxel-resistant strain MCF7/Taxol were cultured,and the expression level of circVAPA,miR-377-3p and ZEB2 were detected and compared.MCF7/Taxol cells were divided into 9 groups.Dual luciferase reporter gene assay was used to detect the targeting relationship between circVAPA and miR-377-3p,and that between miR-377-3p and ZEB2.Cell proliferation inhibition rate was measured by CCK-8 assay and the sensitivity to paclitaxel was assessed. Results The expression levels of circVAPA and ZEB2 in the MCF7/Taxol cells were higher than those in the MCF7 cells,and the expression levels of miR-377-3p were lower than those in the MCF7 cells(P<0.05).The activities of circVAPA and ZEB2 wild-type reporter genes in the miR-377-3p mimic group were both lower than those in the NC group(P<0.05),while there was no significant difference in the activities of circVAPA and ZEB2 mutant reporter genes(P>0.05).Compared with those in the NC group,the paclitaxel sensitivity of the si-circVAPA group and the miR-377-3p mimic group were increased(P<0.05),and the expression level of ZEB2 were decreased(P<0.05).Compared with those in the control plasmid group,the paclitaxel sensitivity in the circVAPA group was decreased,and the expression level of ZEB2 was increased.Compared with those in the circVAPA group,the paclitaxel sensitivity in the circVAPA+miR-377-3p group was increased,and the expression level of ZEB2 was decreased(P<0.05).The paclitaxel sensitivity of MCF7/Taxol cells in the si-circVAPA+miR-377-3p inhibitor group was lower than that in the si-circVAPA group(P<0.05),and the expression level of ZEB2 was higher than that in the si-circVAPA group(P<0.05). Conclusion The regulation of ZEB2 by circular RNA VAPA/miR-377-3p is related to paclitaxel resistance in breast cancer cells.

Key words: breast cancer, paclitaxel resistance, circular RNA vesicle-associated membrane protein-associated protein A, miR-377-3p, Zinc-finger E-box binding homeobox 2

CLC Number:

R737.9

SONG Yunjie, LIANG Jia, XU Bin, ZHANG Penghui, WEI Limin. Effect of circRNA VAPA/miR-377-3p/ZEB2 Axis on Paclitaxel Resistance of Breast Cancer[J]. Journal of Medical Molecular Biology, 2025, 22(6): 579-585.

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