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

Cell Death Dis. 2018 Dec 5;9(12):1167. doi: 10.1038/s41419-018-1220-7.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinogenesis / genetics
  • Carcinogenesis / metabolism
  • Carcinogenesis / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Class I Phosphatidylinositol 3-Kinases / genetics*
  • Class I Phosphatidylinositol 3-Kinases / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Glycogen Synthase Kinase 3 beta / genetics
  • Glycogen Synthase Kinase 3 beta / metabolism
  • Humans
  • Mice
  • Mice, Nude
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / genetics*
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Long Noncoding / antagonists & inhibitors
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Retinoid X Receptor alpha / genetics*
  • Retinoid X Receptor alpha / metabolism
  • Signal Transduction
  • Survival Analysis
  • Triple Negative Breast Neoplasms / genetics*
  • Triple Negative Breast Neoplasms / metabolism
  • Triple Negative Breast Neoplasms / mortality
  • Triple Negative Breast Neoplasms / pathology
  • Xenograft Model Antitumor Assays

Substances

  • DANCR long noncoding RNA, human
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • RXRA protein, human
  • Retinoid X Receptor alpha
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Proto-Oncogene Proteins c-akt