LncCCAT1 Promotes Breast Cancer Stem Cell Function through Activating WNT/β-catenin Signaling

Background: Breast cancer stem cells (BCSCs) play an essential role in facilitating breast cancer relapse and metastasis. The underlying mechanism, however, remains incompletely understood. In the current study, we investigated the clinical significance, biological function and mechanism of a long noncoding RNA CCAT1 (LncCCAT1) in BCSCs. Methods: Firstly, lncRNAs expression in poorly differentiated breast cancer tissues and BCSCs were measured by lncRNA microarray and confirmed in breast cancer tissues and cell lines. The functional roles and mechanisms of LncCCAT1 were further investigated by gain and loss of function assays in vitro and in vivo. Results: LncCCAT1 is markedly upregulated in breast cancer tissues BCSCs and is correlated with poor outcomes in breast cancer patients. Overexpression of LncCCAT1 contributes to the proliferation, stemness, migration and invasion capacities of BCSCs. Mechanistic investigation suggests that LncCCAT1 can interact with miR-204/211, miR-148a/152 and Annexin A2(ANXA2), then upregulate T-cell factor 4 (TCF4) or promote translocation of β-catenin to the nucleus where it activates TCF4, leading to the activation of wingless/integrated (Wnt) signaling. Furthermore, TCF4 can also bind to the promoter of LncCCAT1 to promote LncCCAT1 transcription, thus forming a positive feedback regulatory circuit of LncCCAT1-TCF4-LncCCAT1 in BCSCs. Conclusions: LncCCAT1 plays an important role in breast cancer progression and may serve as a novel target for breast cancer diagnosis and therapy.