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

Po Shun Wang, Cheng Han Chou, Cheng Han Lin, Yun Chin Yao, Hui Chuan Cheng, Hao Yi Li, Yu Chung Chuang, Chia Ning Yang, Luo Ping Ger, Yu Chia Chen, Forn Chia Lin, Tang Long Shen, Michael Hsiao, Pei Jung Lu

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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.

Original languageEnglish
Pages (from-to)4662-4678
Number of pages17
JournalOncogene
Volume37
Issue number34
DOIs
Publication statusPublished - 2018 Aug 23

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All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Wang, P. S., Chou, C. H., Lin, C. H., Yao, Y. C., Cheng, H. C., Li, H. Y., Chuang, Y. C., Yang, C. N., Ger, L. P., Chen, Y. C., Lin, F. C., Shen, T. L., Hsiao, M., & Lu, P. J. (2018). 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(34), 4662-4678. https://doi.org/10.1038/s41388-018-0293-1