Lnc NR2F1-AS1 Promotes Breast Cancer Metastasis by Targeting the MiR-25-3p/ZEB2 Axis

Int J Med Sci. 2023 Jul 24;20(9):1152-1162. doi: 10.7150/ijms.86969. eCollection 2023.

Abstract

Background: Long noncoding RNAs (lncRNAs) substantially affect tumor metastasis and are aberrantly expressed in various cancers. However, its role in breast cancer (BC) remains unclear. Methods: A microarray assay of differentially expressed lncRNAs in epithelial-mesenchymal transition (EMT) and non-EMT cells was performed. The prognostic value of lnc NR2F1-AS1 expression in patients with BC was analyzed using The Cancer Genome Atlas database. Lnc NR2F1-AS1 expression levels in different BC cell lines were assessed using quantitative real-time PCR. The role of lnc NR2F1-AS1 in BC cell metastasis was investigated in vitro and in vivo. Dual luciferase reporter assay and RNA immunoprecipitation were performed to investigate the relationship between lnc NR2F1-AS1, miR-25-3p, and ZEB2. Results: High levels of lnc NR2F1-AS1 were observed in BC cells undergoing EMT and were closely correlated with adverse prognosis in patients with BC. Lnc NR2F1-AS1 knockdown significantly inhibited BC cell migration, invasiveness in vitro, and metastasis in vivo. Mechanistically, lnc NR2F1-AS1 competitively binds to miR-25-3p to impede ZEB2 degradation, a positive EMT transcription factor in BC. Conclusions: Our study revealed a novel lnc NR2F1-AS1/miR-25-3p/ZEB2 axis in BC metastasis and that lnc NR2F1-AS1 may serve as a potential therapeutic target for BC metastasis.

Keywords: Lnc NR2F1-AS1; ZEB2; breast cancer; metastasis; miR-25-3p.

MeSH terms

  • Breast Neoplasms* / pathology
  • COUP Transcription Factor I / genetics
  • COUP Transcription Factor I / metabolism
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • MCF-7 Cells
  • Melanoma, Cutaneous Malignant
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Neoplasms, Second Primary*
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Zinc Finger E-box Binding Homeobox 2 / genetics
  • Zinc Finger E-box Binding Homeobox 2 / metabolism

Substances

  • MicroRNAs
  • RNA, Long Noncoding
  • NR2F1 protein, human
  • COUP Transcription Factor I
  • ZEB2 protein, human
  • Zinc Finger E-box Binding Homeobox 2
  • MIRN25 microRNA, human