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 Differ. 2018 Dec;25(12):2209-2220. doi: 10.1038/s41418-018-0123-6. Epub 2018 May 29.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement
  • Female
  • Humans
  • Mammary Neoplasms, Experimental / diagnostic imaging
  • Mammary Neoplasms, Experimental / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / metabolism*
  • Oligonucleotide Array Sequence Analysis
  • Positron Emission Tomography Computed Tomography
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Receptors, Androgen / metabolism*
  • Triple Negative Breast Neoplasms / diagnostic imaging
  • Triple Negative Breast Neoplasms / metabolism*
  • Tumor Cells, Cultured

Substances

  • AR protein, human
  • MIRN204 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Receptors, Androgen