circVAPA/miR-377-3p/ZEB2轴对乳腺癌紫杉醇耐药的调控作用

doi:10.3870/j.issn.1672-8009.2025.06.007

医学分子生物学杂志 ›› 2025, Vol. 22 ›› Issue (6): 579-585.doi: 10.3870/j.issn.1672-8009.2025.06.007

circVAPA/miR-377-3p/ZEB2轴对乳腺癌紫杉醇耐药的调控作用

宋云杰¹, 梁家², 徐斌¹, 张朋辉¹, 卫利民¹

河南科技大学临床医学院,河南科技大学第一附属医院¹乳腺外科,²胃肠外科河南省洛阳市,471003

收稿日期:2025-02-08 出版日期:2025-11-30 发布日期:2025-12-25
通讯作者: 卫利民(E-mail:13783100995@163.com)
基金资助:
河南省医学科技攻关计划联合共建项目(No.LHGJ20200576)

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

SONG Yunjie¹, LIANG Jia², XU Bin¹, ZHANG Penghui¹, WEI Limin¹

¹Department of Breast Surgery,²Department of Gastrointestinal Surgery,the First Affiliated Hospital of Henan University of Science and Technology,Luoyang,Henan,471003,China

Received:2025-02-08 Online:2025-11-30 Published:2025-12-25
Contact: WEI Limin(E-mail:13783100995@163.com)
Supported by:
Joint Construction Project of Henan Province Medical Science and Technology Research Program(No.LHGJ20200576)

摘要/Abstract

摘要： 目的研究环状RNA囊泡相关膜蛋白相关蛋白A(vesicle-associated membrane protein-associated protein A,circVAPA)靶向miR-377-3p调控锌指E盒结合同源框2(Zinc-finger E-box binding homeobox 2,ZEB2)在乳腺癌紫杉醇耐药中的作用。方法培养人乳腺癌细胞株MCF7及其紫杉醇耐药株MCF7/Taxol,检测其中circVAPA、miR-377-3p、ZEB2的表达。MCF7/Taxol细胞分为对照组、阴性对照(NC)组、si-circVAPA组、miR-377-3p模拟物组、miR-377-3p抑制物组、si-circVAPA+miR-377-3p抑制物组、对照质粒组、circVAPA组、circVAPA+miR-377-3p组。采用双荧光素酶报告基因实验检测circVAPA靶向miR-377-3p、miR-377-3p靶向ZEB2的情况,采用CCK-8法检测细胞增殖抑制率并评估紫杉醇敏感性。结果 MCF7/Taxol细胞中circVAPA、ZEB2的表达水平高于MCF7细胞,miR-377-3p的表达水平低于MCF7细胞(P<0.05)。miR-377-3p模拟物组MCF7/Taxol细胞中circVAPA和ZEB2野生型报告基因的活性均低于NC组(P<0.05),circVAPA和ZEB2突变型报告基因的活性与NC组比较无显著差异(P>0.05)。si-circVAPA组和miR-377-3p模拟物组MCF7/Taxol细胞的紫杉醇敏感性高于NC组(P<0.05),ZEB2的表达水平低于NC组(P<0.05)。circVAPA组的紫杉醇敏感性低于对照质粒组,ZEB2的表达水平高于对照质粒组;circVAPA+miR-377-3p组的紫杉醇敏感性高于circVAPA组,ZEB2的表达水平低于circVAPA组(P<0.05)。si-circVAPA+miR-377-3p抑制物组MCF7/Taxol细胞的紫杉醇敏感性低于si-circVAPA组(P<0.05),ZEB2的表达水平高于si-circVAPA组(P<0.05)。结论 circVAPA靶向miR-377-3p调控ZEB2与乳腺癌细胞紫杉醇耐药相关。

关键词: 乳腺癌, 紫杉醇耐药, 环状RNA囊泡相关膜蛋白相关蛋白A, miR-377-3p, 锌指E盒结合同源框2

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

中图分类号:

R737.9

宋云杰, 梁家, 徐斌, 张朋辉, 卫利民. circVAPA/miR-377-3p/ZEB2轴对乳腺癌紫杉醇耐药的调控作用[J]. 医学分子生物学杂志, 2025, 22(6): 579-585.

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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circVAPA/miR-377-3p/ZEB2轴对乳腺癌紫杉醇耐药的调控作用

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

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