Long Non-coding RNA NR2F1-AS1 Induces Breast Cancer Dormancy in Lungs by Regulating NR2F1 and ?Np63

We show that the epithelial-like and mesenchymal-like subpopulations of breast cancer stem-like cells (BCSCs) demonstrate different levels dormancy and tumorigenicity in lungs. The long non-coding RNA (lncRNA) molecule NR2F1-AS1 (NAS1) is up-regulated in the dormant BCSC subpopulation, and functionally promotes tumor dissemination but reduces proliferation in lungs. Mechanically, NAS1 promotes internal ribosome entry site (IRES)-mediated NR2F1 translation, leading to inhibition of ?Np63 transcription by NR2F1. Further, ?Np63 downregulation results in epithelial-mesenchymal transition, reduced tumorigenicity and enhanced dormancy of cancer cells in lungs. Overall design: Transcriptomic sequencing was firstly performed in MCF10 breast cancer cell line series that include MCF10AT, MCF10CA1h, MCF10CA1a, CA1h-P1 (CD24-CD44med subpopulation of MCF10CA1h) and CA1h-P2 (CD24-CD44high subpopulation of MCF10CA1h), while MCF10CA1h and CA1h-P2 were identified with dormant characteristics. We found that the long non-coding RNA (lncRNA) molecule NR2F1-AS1 (NAS1) is up-regulated in the dormant cells. Then the transcriptomes of CA1h-P2 with NAS1 knockdown, MCF10CA1h and MCF7 with NR2F1 overexpression, and their respective controls were sequenced to find the molecules affected by both NAS1 and NR2F1.