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Knockdown of miR-221 promotes the cisplatin-inducing apoptosis by targeting the BIM-Bax/Bak axis in breast cancer

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Tumor Biology

Abstract

Accumulating evidence shows that microRNAs (miRNAs) have a critical role in the initiation and progression of types of human cancer, including breast cancer. Recent research indicated that miRNAs are also related with the chemotherapy on cancers. In this study, the expression of miR-221 in breast cancer (BC) patients’ serum and cancer tissues was found to be significantly up-regulated. The results of in vitro MTT assay indicated that although the anti-miR-221 oligonucleotide alone did not influence the viability of BC cell lines markedly, it significantly promoted the cytotoxicity of cisplatin (DDP) to BC cells. Mechanistic studies demonstrated that the gene of BIM (Bcl-2 interacting mediator of cell death), a pro-apoptotic Bcl-2 family protein, was up-regulated by the knockdown of miR-221. We found that the synergetic effect of anti-miR-221 on increasing the sensitivity of MDA-MB-231 was BIM dependant. Furthermore, results of immunoprecipitation showed the up-regulated BIM directly combined with the Bax and Bak, leading to mitochondrial dysfunction. Our results suggest the anti-miR-221 could promote the cisplatin-inducing apoptosis by targeting the Bim-Bax/Bak axis in breast cancer.

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Acknowledgments

This work was supported by Wenzhou Science and Technology Bureau (Grant numbers Y20100008)

Author contributions

GH designed the study. ZY wrote the manuscript. RH performed out the western blot and immunoprecipitation. ZY, YC, and XW carried out the cell culture and transfection, RT-PCR, and flow cytometry. All authors approved the final version of the manuscript.

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Authors and Affiliations

  1. Department of Surgical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou City, Zhejiang Province, China, 325000

    Zhiqiang Ye, Rutian Hao, Yefeng Cai, Xiaobo Wang & Guanli Huang

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  1. Zhiqiang Ye
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  2. Rutian Hao
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  3. Yefeng Cai
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  4. Xiaobo Wang
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  5. Guanli Huang
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Corresponding author

Correspondence to Guanli Huang.

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The study was approved by Ethic Committee of the First Affiliated Hospital of Wenzhou Medical University.

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Ye, Z., Hao, R., Cai, Y. et al. Knockdown of miR-221 promotes the cisplatin-inducing apoptosis by targeting the BIM-Bax/Bak axis in breast cancer. Tumor Biol. 37, 4509–4515 (2016). https://doi.org/10.1007/s13277-015-4267-4

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  • DOI: https://doi.org/10.1007/s13277-015-4267-4

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