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MicroRNA-218 regulates cisplatin (DPP) chemosensitivity in non-small cell lung cancer by targeting RUNX2

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Tumor Biology

Abstract

Downregulation of microRNA-218 (miR-218) is found in various human cancers, including non-small cell lung cancer (NSCLC). However, the involvement of chemosensitivity to cisplatin (DDP) and the underlying molecular mechanism remain unclear. In this study, we investigate whether miR-218 mediates NSCLC cell functions associated with chemoresistance. Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to detect miR-218 expression in NSCLC cell lines A549/DDP and/or A549. The cell activity was measured by MTT assay. Cell cycle and cell apoptosis were detected by flow cytometry. Luciferase reporter assays and Western blots were used to validate runt-related transcription factor 2 (RUNX2) as a direct target gene of miR-218. miR-218 was significantly reduced in A549/DDP cells compared with parent A549 cells. Upregulation of miR-218 altered cell cycle-induced cell apoptosis and enhanced the sensitivity of A549/DDP cells to cisplatin. Mechanistically, RUNX2 was identified as a direct and functional target of miR-218, and RUNX2 executed the former on lung cancer chemoresistance. Our present study demonstrated for the first time that downregulation of miR-218 may contribute to the chemoresistance of NSCLC cells to cisplatin, which leads to upregulation of RUNX2. Uncovering the mechanism represents a novel approach to enhance the efficacy of chemotherapy during cancer treatment.

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Acknowledgments

This study was supported by the health system advanced appropriate technology promotion project of Shanghai in China (2013SY036).

Conflicts of interest

The authors declare that there are no conflicts of interest.

Authors’ contributions

JX, FY, and LZW conceived and designed the experiments. JX and ZXC performed the experiments. JX, DL, and FY analyzed the data. ZW and ZXC contributed the reagents/materials/analysis tools. JX wrote the paper. LZW and ZXC reviewed the manuscript.

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    Authors and Affiliations

    1. Department of Nuclear, Shanghai Tenth People’s Hospital, Tongji University, School of Medicine, Shanghai, China

      Jing Xie, Fei Yu, Dan Li, Xuchao Zhu, Xiaoping Zhang & Zhongwei Lv

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    1. Jing Xie
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    2. Fei Yu
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    3. Dan Li
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    4. Xuchao Zhu
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    5. Xiaoping Zhang
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    6. Zhongwei Lv
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    Correspondence to Xiaoping Zhang or Zhongwei Lv.

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    Jing Xie, Fei Yu and Dan Li contributed equally to this work.

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    Xie, J., Yu, F., Li, D. et al. MicroRNA-218 regulates cisplatin (DPP) chemosensitivity in non-small cell lung cancer by targeting RUNX2. Tumor Biol. 37, 1197–1204 (2016). https://doi.org/10.1007/s13277-015-3831-2

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    • DOI: https://doi.org/10.1007/s13277-015-3831-2

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