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MicroRNA-224 通过凋亡抑制因子 5 调节乳腺癌细胞对多西他赛的化疗敏感性。

MicroRNA-224 modulates chemosensitivity of breast cancer cells to docetaxel by apoptosis inhibitor 5.

机构信息

First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, 210029, China.

出版信息

J BUON. 2021 Mar-Apr;26(2):450-458.

PMID:34076992
Abstract

PURPOSE

The view that microRNA-224 (miR-224) may lead to tumorigenesis has been accepted in many studies. However, its role remains unclear in modulating the chemosensitivity of breast cancer cells to docetaxel (DOC). Thus, the aim of this study was to estimate what's the role of miR-224 in the chemosensitivity of breast cancer cells to DOC.

METHODS

The role of miR-224 in breast cancer cells was analyzed using CCK-8 assay, real-time PCR, flow cytometry assay and Western blot. Dual-luciferase reporter assay and API-5-siRNA technology were performed to analyze the association between miR-224 and Apoptosis inhibitor 5 (API-5).

RESULTS

Overexpression of miR-224 could significantly decrease the chemosensitivity of MCF-7 breast cancer cells to DOC. The luciferase activity of MCF-7/DOC cells containing wild-type 3'UTR of API-5 could be inhibited by miR-224 mimics. Similarly, the chemoresistance of MCF-7 cells to DOC induced by miR-224 mimics could be partially reversed by API-5-siRNA.

CONCLUSION

An inverse association between miR-224 and API-5 in breast cancer cells was revealed. Dysregulation of miR-224 plays a vital role in the acquired DOC resistance of breast cancer and at least partially via targeting API-5.

摘要

目的

许多研究都认为 microRNA-224(miR-224)可能导致肿瘤发生。然而,其在调节乳腺癌细胞对多西紫杉醇(DOC)化疗敏感性中的作用仍不清楚。因此,本研究旨在评估 miR-224 在乳腺癌细胞对 DOC 化疗敏感性中的作用。

方法

使用 CCK-8 测定法、实时 PCR、流式细胞术测定法和 Western blot 分析 miR-224 在乳腺癌细胞中的作用。双荧光素酶报告基因测定法和 API-5-siRNA 技术用于分析 miR-224 与凋亡抑制剂 5(API-5)之间的关联。

结果

过表达 miR-224 可显著降低 MCF-7 乳腺癌细胞对 DOC 的化疗敏感性。MCF-7/DOC 细胞中包含野生型 3'UTR 的 API-5 的荧光素酶活性可被 miR-224 模拟物抑制。同样,miR-224 模拟物诱导的 MCF-7 细胞对 DOC 的化学耐药性可部分被 API-5-siRNA 逆转。

结论

揭示了乳腺癌细胞中 miR-224 与 API-5 之间的负相关关系。miR-224 的失调在乳腺癌获得性 DOC 耐药中起重要作用,至少部分通过靶向 API-5 起作用。

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