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Abstact  Conventional therapies and novel molecular targeted therapies against breast cancer have gained great advances over the past two decades. However, poor prognosis and low survival rate are far from expectation for improvement, particularly in patients with triple negative breast cancer (TNBC). Here, we found that lncRNA  DANCR  was significantly overregulated in TNBC tissues and cell lines compared with normal breast tissues or other type of breast cancer. Knockdown of  DANCR  suppressed TNBC proliferation both in vitro and in vivo. Further study of underlying mechanisms demonstrated that  DANCR  bound with RXRA and increased its serine 49/78 phosphorylation via GSK3β, resulting in activating PIK3CA transcription, and subsequently enhanced PI3K/AKT signaling and TNBC tumorigenesis. Taken together, Our findings identified  DANCR  as an pro-oncogene and uncoverd a new working pattern of lncRNA to mediate TNBC tumorigenesis, which may be a potential therapeutic target for improving treatment of TNBC.

LncRNA DANCR upregulates PI3K/AKT signaling through activating serine phosphorylation of RXRA