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MiR-145 promotes TNF-α-induced apoptosis by facilitating the formation of RIP1-FADDcaspase-8 complex in triple-negative breast cancer

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Tumor Biology

Abstract

Researches indicate that the dysregulation of microRNA (miRNA) is involved in tumorigenesis. Among such dysregulated miRNAs in cancer, miR-145 is reported to be downregulated in multiple cancers. In this study, we demonstrated the downregulation of miR-145 in triple-negative breast cancer (TNBC) tissues and TNBC cell lines by quantitative reverse-transcription polymerase chain reaction (RT-PCR) analysis. Furthermore, we found that the tumor necrosis factor-alpha (TNF-α)-induced apoptosis was expanded by the transfection of miR-145 in MDA-MB-231 which belongs to the TNBC cell lines. We then indicated that the mechanism by which miR-145 promotes the TNF-α-induced apoptosis is dependent on the formation of RIP1-FADD-caspase-8 complex. The cellular inhibitor of apoptosis (cIAP1), which is the inhibitor of apoptosis protein, was found to be a target of miR-145 in MDA-MB-231 cells. As a result of cIAP1 overexpression, the promotion of miR-145 on TNF-α-induced apoptosis was inhibited in MDA-MB-231 cells. Therefore, our results indicate that miR-145 acts as a tumor suppressor in TNBC, suggesting that the miR-145-cIAP1 axis might be a potential therapeutic target for TNBC.

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Acknowledgments

This study is supported by the Central Laboratory of The Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University and the School of Laboratory Medicine and Life Science affiliated to Wenzhou Medical University.

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Authors and Affiliations

  1. Department of Breast Surgery, The Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, 325027, China

    Min Zheng & Zhihao Wu

  2. School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, 325035, China

    Anqi Wu, Zhenyu Huang & Na He

  3. Department of Breast Surgery, Zhejiang Provincial Hospital of Traditional Chinese Medicine, No. 54 Youdian Road, Hangzhou City, Zhejiang Province, 310006, China

    Xiaohong Xie

Authors
  1. Min Zheng
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  2. Zhihao Wu
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  3. Anqi Wu
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  4. Zhenyu Huang
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  5. Na He
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  6. Xiaohong Xie
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Corresponding author

Correspondence to Xiaohong Xie.

Ethics declarations

All samples were collected with patients’ informed consent, and this project was approved by the Ethics Committee of The Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University.

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Zheng, M., Wu, Z., Wu, A. et al. MiR-145 promotes TNF-α-induced apoptosis by facilitating the formation of RIP1-FADDcaspase-8 complex in triple-negative breast cancer. Tumor Biol. 37, 8599–8607 (2016). https://doi.org/10.1007/s13277-015-4631-4

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  • DOI: https://doi.org/10.1007/s13277-015-4631-4

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