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A novel long non-coding RNA linc-ZNF469-3 promotes lung metastasis through miR-574-5p-ZEB1 axis in triple negative breast cancer

Oncogene volume 37, pages 4662–4678 (2018)Cite this article

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Abstract

Triple-negative breast cancer (TNBC) patients usually lead to poor prognosis and survival because of metastasis. The major sites for TNBC metastasis include the lungs, brain, liver, and bone. Long non-coding RNAs (lncRNAs) are non-protein-coding transcripts longer than 200 nucleotides and have been reported as important regulators in BC metastasis. However, the underlying mechanisms for lncRNAs regulating TNBC metastasis are not fully understood. Here we found that linc-ZNF469-3 was highly expressed in lung-metastatic LM2-4175 TNBC cells and overexpression of linc-ZNF469-3 enhanced invasion ability and stemness properties in vitro and lung metastasis in vivo. Furthermore, we found linc-ZNF469-3 physically interacted with miR-574-5p and overexpression of miR-574-5p attenuated ZEB1 expression. Importantly, endogenous high expressions of linc-ZNF469-3 and ZEB1 were correlated with tumor recurrence in TNBC patients with lung metastasis. Taken together, our findings suggested that linc-ZNF469-3 promotes lung metastasis of TNBC through miR-574-5p-ZEB1 signaling axis and may be used as potential prognostic marker for TNBC patients.

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Acknowledgements

This work was supported by the Ministry of Science and Technology [MOST 103-2320-B-006-048 and MOST 105-2320-B-006-054 to PJL] and National Cheng Kung University Hospital [NCKUH-10605012 and NCKUH-10601003 to FCL and PJL]. Academia Sinica and Ministry of Science and Technology [MOST106-0210-01-15-02, MOST 107-0210-01-19-01 to Michael Hsiao]. Funding for open access charge: Ministry of Science and Technology [MOST 103-2320-B-006-048 and MOST 105-2320-B-006-054]. We thank the National Center for Genome Medicine for assisting with RNA sequencing and the Center for Genome Medicine, National Cheng Kung University for the support of lncRNA annotation and bioinformatic analyses. We also thank Dr. Myriam Gorospe (National Institutes of Health, Baltimore, MD, USA) for the plasmid pMS2 (24 × ), pMS2-lincRNA-p21, and pMS2-GST, and Dr. Tang-Long Shen (National Taiwan University, Taipei, Taiwan) for MDA-MB-231 cell lines including parental, LM2-4175, BrM-831, and BoM-1833.

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    1. Institute of Clinical Medicine, Medical College, National Cheng Kung University, Tainan, 70403, Taiwan

      Po-Shun Wang, Cheng-Han Chou, Cheng-Han Lin, Yun-Chin Yao, Hui-Chuan Cheng, Hao-Yi Li & Pei-Jung Lu

    2. Department of Life Sciences, National University of Kaohsiung, Kaohsiung, 81148, Taiwan

      Yu-Chung Chuang & Chia-Ning Yang

    3. Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, 81362, Taiwan

      Luo-Ping Ger

    4. Departments of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, 81362, Taiwan

      Yu-Chia Chen

    5. Department of Radiation Oncology, National Cheng Kung University Hospital, Tainan, 70403, Taiwan

      Forn-Chia Lin

    6. Department of Plant Pathology and Microbiology, National Taiwan University, Taipei, 10617, Taiwan

      Tang-Long Shen

    7. Genomics Research Center, Academia Sinica, Taipei, 11529, Taiwan

      Michael Hsiao

    8. Department of Biochemistry, College of Medicine, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan

      Michael Hsiao

    9. Department of Clinical Medicine Research, National Cheng Kung University Hospital, Tainan, 70403, Taiwan

      Pei-Jung Lu

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    Wang, PS., Chou, CH., Lin, CH. et al. A novel long non-coding RNA linc-ZNF469-3 promotes lung metastasis through miR-574-5p-ZEB1 axis in triple negative breast cancer. Oncogene 37, 4662–4678 (2018). https://doi.org/10.1038/s41388-018-0293-1

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