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MiR-145 regulates cancer stem-like properties and epithelial-to-mesenchymal transition in lung adenocarcinoma-initiating cells

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Tumor Biology

Abstract

MicroRNA-145 (MiR-145) is an important regulator of tumorigenesis. Our previous work indicated that miR-145 reduced the proliferation and invasion as well as the tumorosphere growth capacity in lung adenocarcinoma cells. However, the underlying molecular mechanisms remain elusive. Here, we reported that the expression level of miR-145 was downregulated in lung adenocarcinoma tissues and negatively correlated with the expression level of Oct4. MiR-145 inhibited the proliferation of lung cancer-initiating cells (LCICs), partially by regulating Oct4 expression. Furthermore, we found that miR-145 exerted repressive effect on cancer stem cell properties and inhibited epithelial-mesenchymal transition (EMT) in vitro, also partially by regulating Oct4. Finally, we confirmed the repressive effect of miR-145 on cancer stem cell properties and EMT in vivo. Taken together, these evidences suggest that miR-145 serves as a tumor suppressor which downregulates LCICs’ cancer stem cell properties and EMT process by targeting Oct4, leading to the inhibition of tumor growth and metastasis.

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Conflicts of interest

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Founding sources

This study is founded by the Natural Science Foundation of China (81372321, 81201830), University Grant of Jiangsu Province (13KJB320010), and Key Clinical Medicine Technology Foundation of Jiangsu Province (BL2012030).

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Authors and Affiliations

  1. Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Baiziting 42, Nanjing, 210009, China

    Jingwen Hu, Mantang Qiu, Feng Jiang, Shuai Zhang, Xin Yang, Jie Wang, Lin Xu & Rong Yin

  2. Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, 210009, China

    Jingwen Hu, Mantang Qiu, Feng Jiang, Shuai Zhang, Xin Yang, Lin Xu & Rong Yin

  3. The Fourth Clinical College, Nanjing Medical University, Nanjing, 210029, China

    Mantang Qiu

  4. The First Clinical College, Nanjing Medical University, Nanjing, 210029, China

    Xin Yang

  5. Department of Scientific Research, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, 210009, China

    Jie Wang

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  1. Jingwen Hu
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  2. Mantang Qiu
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  3. Feng Jiang
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  4. Shuai Zhang
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  5. Xin Yang
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  6. Jie Wang
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  7. Lin Xu
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  8. Rong Yin
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Corresponding authors

Correspondence to Lin Xu or Rong Yin.

Additional information

Jingwen Hu and Mantang Qiu contributed equally to this work.

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Hu, J., Qiu, M., Jiang, F. et al. MiR-145 regulates cancer stem-like properties and epithelial-to-mesenchymal transition in lung adenocarcinoma-initiating cells. Tumor Biol. 35, 8953–8961 (2014). https://doi.org/10.1007/s13277-014-2158-8

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  • DOI: https://doi.org/10.1007/s13277-014-2158-8

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