title: Transforming Growth Factor-β-Induced RBFOX3 Inhibition Promotes Epithelial-Mesenchymal Transition of Lung Cancer Cells.
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-β (TGF-β) signaling pathway is important in cancer progression, we investigated its role in RBFOX3 expression in A549 lung adenocarcinoma cells. TGF-β1 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-β1-induced EMT. In immunofluorescence microscopic analysis, mesenchymal morphology was more prominent in RBFOX3-depleted cells than in control cells. These findings show that TGF-β-induced RBFOX3 inhibition plays an important role in EMT and propose a novel role for RBFOX3 in cancer progression.
authors.affiliation: Department of Biochemistry, Chungnam National University, Daejeon 34134, Korea.
authors.forename: Yong-Eun
authors.initials: YE
authors.lastname: Kim
authors.affiliation: Department of Pathology, Daejeon Saint Mary's Hospital, The Catholic University of Korea, Daejeon 34943 Korea.
authors.forename: Jong Ok
authors.initials: JO
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, Chungnam National University, Daejeon 34134, Korea.
authors.forename: Ki-Sun
authors.initials: KS
authors.lastname: Park
authors.affiliation: Department of Pharmacology, College of Medicine, Chungnam National University, Daejeon 35015, Korea.
authors.forename: Minho
authors.initials: M
authors.lastname: Won
authors.affiliation: Department of Biochemistry, Chungnam National University, Daejeon 34134, Korea.
authors.forename: Kyoon Eon
authors.initials: KE
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, Chungnam National University, Daejeon 34134, Korea.
authors.forename: Kee K
authors.initials: KK
authors.lastname: Kim
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism*; D000077192:Adenocarcinoma of Lung; D034961:Antigens, Nuclear / Q000235:genetics / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D063646:Carcinogenesis / Q000235:genetics; D045744:Cell Line, Tumor; D062445:Claudin-1 / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D012326:RNA Splicing / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D020545:Respiratory Mucosa / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D034961:Antigens, Nuclear; D015820:Cadherins; D062445:Claudin-1; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D016212:Transforming Growth Factor beta; C506808:neuronal nuclear antigen NeuN, human
keywords: EMT; RNA-binding protein; Rbfox family; Rbfox3; lung cancer