Open AccessLong noncoding RNA NORAD regulates transforming growth factor‐β signaling and epithelial‐to‐mesenchymal transition‐like phenotype
Author(s) -
Kawasaki Natsumi,
Miwa Toshiki,
Hokari Satoshi,
Sakurai Tsubasa,
Ohmori Kazuho,
Miyauchi Kensuke,
Miyazono Kohei,
Koinuma Daizo
Publication year - 2018
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13626
Subject(s) - gene knockdown , epithelial–mesenchymal transition , transforming growth factor , long non coding rna , biology , smad , microbiology and biotechnology , phenotype , rna binding protein , rna , transforming growth factor beta , cancer research , importin , downregulation and upregulation , nuclear transport , cytoplasm , cell nucleus , genetics , gene
Long noncoding RNA s 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 ( PUM 1/ PUM 2). 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, PUM 1 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.