Oncotarget

Research Papers:

Overexpression of miR-489 enhances efficacy of 5-fluorouracil-based treatment in breast cancer stem cells by targeting XIAP

Xuedong Wang, Xinguo Wang, Juan Gu _, Ming Zhou, Zhimin He, Xinhui Wang and Soldano Ferrone

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Oncotarget. 2017; 8:113837-113846. https://doi.org/10.18632/oncotarget.22985

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Abstract

Xuedong Wang1,2,5, Xinguo Wang1,2, Juan Gu1,2, Ming Zhou3, Zhimin He4, Xinhui Wang5 and Soldano Ferrone5

1Department of Medical Laboratory Science, The Fifth People’s Hospital of Wuxi, The Medical School of Jiangnan University, Wuxi, Jiangsu 214005, China

2Department of Pathology, The Fifth People’s Hospital of Wuxi, Nanjing Medical University, Wuxi, Jiangsu 214005, China

3Cancer Research Institute, Central South University, Changsha, Hunan 410078, China

4Cancer Hospital and Cancer Research Institute, Guangzhou Medical University, Guangzhou, Guangdong 510095, China

5Department of Medical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA

Correspondence to:

Juan Gu, email: gujuan1018@126.com

Keywords: BCSCs; miR-489; 5-fluorouracil; resistance; XIAP

Received: August 28, 2017     Accepted: November 17, 2017     Published: December 06, 2017

ABSTRACT

Population of cancer stem cells (CSCs) in breast cancer is reported to be resistant to chemotherapy. Furthermore, many cases of treatment failure are induced by the chemoresistance of CSCs in breast cancer patients. Therefore, novel strategies should be explored urgently to reverse drug-resistance in breast cancer stem cells (BCSCs). In this study, we isolated and cultured the BCSCs from the T-47D and SKBR3 breast cancer cell lines. We observed significant resistance to 5-fluorouracil in BCSCs. Mechanically, we found that expression of miR-489 was decreased in BCSCs. Furthermore, overexpression of miR-489 was found to increase the cytotoxicity of 5-fluorouracil to BCSCs. XIAP, a key anti-apoptotic protein, was proved to be the target of miR-489. We found that enforced expression of XIAP through its recombinant expression vector abolished the effect of miR-489 on reversing the 5-fluorouracil resistance. On the contrary, embelin, a XIAP specific inhibitor, was found to sensitize BCSCs to 5-fluorouracil similarly with miR-489. In summary, our data demonstrate that introduction with miR-489 represents a novel strategy to enhance efficacy of 5-fluorouracil-based treatment in BCSCs.


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