Long noncoding RNA NORAD regulates transforming growth factor-β signaling and epithelial-to-mesenchymal transition-like phenotype

Cancer Sci. 2018 Jul;109(7):2211-2220. doi: 10.1111/cas.13626. Epub 2018 May 29.


Long noncoding RNAs are involved in a variety of cellular functions. In particular, an increasing number of studies have revealed the functions of long noncoding RNA in various cancers; however, their precise roles and mechanisms of action remain to be elucidated. NORAD, a cytoplasmic long noncoding RNA, is upregulated by irradiation and functions as a potential oncogenic factor by binding and inhibiting Pumilio proteins (PUM1/PUM2). Here, we show that NORAD upregulates transforming growth factor-β (TGF-β) signaling and regulates TGF-β-induced epithelial-to-mesenchymal transition (EMT)-like phenotype, which is a critical step in the progression of lung adenocarcinoma, A549 cells. However, PUM1 does not appear to be involved in this process. We thus focused on importin β1 as a binding partner of NORAD and found that knockdown of NORAD partially inhibits the physical interaction of importin β1 with Smad3, inhibiting the nuclear accumulation of Smad complexes in response to TGF-β. Our findings may provide a new mechanism underlying the function of NORAD in cancer cells.

Keywords: epithelial-to-mesenchymal transition; long noncoding RNA; non-small-cell lung cancer; nuclear transport; transforming growth factor-β.

MeSH terms

  • A549 Cells
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Epithelial-Mesenchymal Transition / physiology*
  • Gene Expression Regulation, Neoplastic / physiology
  • Humans
  • Lung Neoplasms / pathology*
  • Phenotype
  • RNA, Long Noncoding / metabolism*
  • Signal Transduction
  • Transforming Growth Factor beta1 / metabolism*


  • NORAD long non-coding RNA, human
  • RNA, Long Noncoding
  • TGFB1 protein, human
  • Transforming Growth Factor beta1