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Transforming Growth Factor-β-Induced RBFOX3 Inhibition Promotes Epithelial-Mesenchymal Transition of Lung Cancer Cells

  • Kim, Yong-Eun (Department of Biochemistry, Chungnam National University) ;
  • Kim, Jong Ok (Department of Pathology, Daejeon Saint Mary's Hospital, The Catholic University of Korea) ;
  • Park, Ki-Sun (Department of Biochemistry, Chungnam National University) ;
  • Won, Minho (Department of Pharmacology, College of Medicine, Chungnam National University) ;
  • Kim, Kyoon Eon (Department of Biochemistry, Chungnam National University) ;
  • Kim, Kee K. (Department of Biochemistry, Chungnam National University)
  • Received : 2016.06.16
  • Accepted : 2016.07.07
  • Published : 2016.08.31

Abstract

The RNA-binding protein Rbfox3 is a well-known splicing regulator that is used as a marker for post-mitotic neurons in various vertebrate species. Although recent studies indicate a variable expression of Rbfox3 in non-neuronal tissues, including lung tissue, its cellular function in lung cancer remains largely unknown. Here, we report that the number of RBFOX3-positive cells in tumorous lung tissue is lower than that in normal lung tissue. As the transforming growth factor-${\beta}$ (TGF-${\beta}$) signaling pathway is important in cancer progression, we investigated its role in RBFOX3 expression in A549 lung adenocarcinoma cells. TGF-${\beta}1$ treatment inhibited RBFOX3 expression at the transcriptional level. Further, RBFOX3 depletion led to a change in the expression levels of a subset of proteins related to epithelial-mesenchymal transition (EMT), such as E-cadherin and Claudin-1, during TGF-${\beta}1$-induced EMT. In immunofluorescence microscopic analysis, mesenchymal morphology was more prominent in RBFOX3-depleted cells than in control cells. These findings show that TGF-${\beta}$-induced RBFOX3 inhibition plays an important role in EMT and propose a novel role for RBFOX3 in cancer progression.

Acknowledgement

Supported by : Chungnam National University

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