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Jagged2 通过调控 microRNA-200 促进三阴性乳腺癌细胞的肿瘤干细胞特性和紫杉醇耐药性。

Jagged2 promotes cancer stem cell properties of triple negative breast cancer cells and paclitaxel resistance via regulating microRNA-200.

机构信息

Department of Oncological Surgery, Fujian Medical University Affiliated MinDong Hospital, Fuan, China.

出版信息

Eur Rev Med Pharmacol Sci. 2018 Sep;22(18):6008-6014. doi: 10.26355/eurrev_201809_15936.

DOI:10.26355/eurrev_201809_15936
PMID:30280784
Abstract

OBJECTIVE

To investigate the role of Jagged2 in triple negative breast cancer (TNBC) and its underlying mechanism.

PATIENTS AND METHODS

Breast cancer tissues of patients diagnosed with TNBC in Fujian Medical University Affiliated MinDong Hospital from January 2015 to September 2017 were selected. TNBC patients were divided into the paclitaxel-resistant group (n=34) and non-resistance group (n=11). Jagged2 expression in paclitaxel-resistant group and non-resistance group before and after treatment was detected by quantitative Real-time-polymerase chain reaction (qRT-PCR), respectively. After Jagged2 knockdown in paclitaxel-resistant MDA-MB-231 cells (MDA-MB-231/TXR), expression of CD44+CD24-ESA+ subset was detected by flow cytometry. MicroRNA-200 expression was detected after Jagged2 knockdown in MDA-MB-231/TXR cells.

RESULTS

Jagged2 was highly expressed in paclitaxel-resistant TNBC tissues and cells. Jagged2 expression was found to be associated with cancer stem cell (CSC) properties of TNBC cells. Knockdown of Jagged2 inhibited CSC properties and paclitaxel resistance, whereas upregulated microRNA-200 expression. The inhibited CSC properties and paclitaxel resistance induced by Jagged2 knockdown were reversed by microRNA-200 knockdown.

CONCLUSIONS

Jagged2 maintains CSC properties of TNBC cells and paclitaxel resistance via regulating microRNA-200.

摘要

目的

探讨 Jagged2 在三阴性乳腺癌(TNBC)中的作用及其机制。

患者与方法

选取 2015 年 1 月至 2017 年 9 月福建医科大学附属闽东医院诊断为 TNBC 的患者的乳腺癌组织。将 TNBC 患者分为紫杉醇耐药组(n=34)和非耐药组(n=11)。分别采用定量实时聚合酶链反应(qRT-PCR)检测紫杉醇耐药组和非耐药组治疗前后 Jagged2 的表达。在紫杉醇耐药 MDA-MB-231 细胞(MDA-MB-231/TXR)中敲低 Jagged2 后,采用流式细胞术检测 CD44+CD24-ESA+亚群的表达。在 MDA-MB-231/TXR 细胞中敲低 Jagged2 后检测 microRNA-200 的表达。

结果

Jagged2 在紫杉醇耐药的 TNBC 组织和细胞中高表达。Jagged2 的表达与 TNBC 细胞的癌干细胞(CSC)特性有关。敲低 Jagged2 抑制 CSC 特性和紫杉醇耐药,而上调 microRNA-200 的表达。敲低 Jagged2 诱导的 CSC 特性和紫杉醇耐药被 microRNA-200 的敲低所逆转。

结论

Jagged2 通过调节 microRNA-200 维持 TNBC 细胞的 CSC 特性和紫杉醇耐药性。

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