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An androgen receptor negatively induced long non-coding RNA ARNILA binding to miR-204 promotes the invasion and metastasis of triple-negative breast cancer

Cell Death & Differentiation (2018) | Download Citation

Abstract

Androgen receptor (AR) is emerging as a novel prognostic biomarker in triple-negative breast cancer (TNBC), but the underlying mechanisms remain unknown. As accumulating evidence has shown that long non-coding RNAs (lncRNAs) regulate important cancer hallmarks, we hypothesised that AR-regulated lncRNAs might play roles in TNBC progression. Here, we performed experiments with or without DHT treatment in three TNBC cell lines, and we identified an AR negatively induced lncRNA (ARNILA), which correlated with poor progression-free survival (PFS) in TNBC patients and promoted epithelial−mesenchymal transition (EMT), invasion and metastasis in vitro and in vivo. Subsequently, we demonstrated that ARNILA functioned as a competing endogenous RNA (ceRNA) for miR-204 to facilitate expression of its target gene Sox4, which is known to induce EMT and contribute to breast cancer progression, thereby promoting EMT, invasion and metastasis of TNBC. Our findings not only provide new insights into the mechanisms of lncRNA in regulating AR but also suggest ARNILA as an alternative therapeutic target to suppress metastasis of TNBC patients.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 81773102, No. 81470357) and a Foundation for Clinical Medicine Science and Technology Special Project of the Jiangsu Province, China (No. BL2014071) (to XG).

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Author notes

  1. Edited by RA Knight.

Affiliations

  1. Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China

    • Fang Yang
    • , Yan Shen
    • , Wenwen Zhang
    • , Juan Jin
    • , Doudou Huang
    • , Hehui Fang
    • , Yaqin Shi
    • , Lin Tang
    • , Weiwei Chen
    •  & Xiaoxiang Guan
  2. Department of Medical Oncology, Jinling Clinical College of Nanjing Medical University, Nanjing, China

    • Wenfei Ji
    •  & Xiaoxiang Guan
  3. Department of Pharmacology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China

    • Guohua Zhou
  4. Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China

    • Xiaoxiang Guan

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The authors declare that they have no conflict of interest.

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Correspondence to Xiaoxiang Guan.

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DOI

https://doi.org/10.1038/s41418-018-0123-6