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

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- (TGF-) signaling and regulates TGF--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 1 as a binding partner of NORAD and found that knockdown of NORAD partially inhibits the physical interaction of importin 1 with Smad3, inhibiting the nuclear accumulation of Smad complexes in response to TGF-. Our findings may provide a new mechanism underlying the function of NORAD in cancer cells.