title: EGF-induced C/EBPβ participates in EMT by decreasing the expression of miR-203 in esophageal squamous cell carcinoma cells.
abstract: Epithelial-mesenchymal transition (EMT) is a developmental program that is associated with esophageal squamous cell carcinoma (ESCC) progression and metastasis. Recently, C/EBPβ has been reported to be an EMT inducer in cancer. However, the detailed molecular mechanisms remain unclear. Here, we report for the first time, that the truncated CCAAT-enhancer-binding protein β (C/EBPβ) LIP isoform is abnormally overexpressed and correlated with cancer metastasis in clinical specimens of human ESCC. Furthermore, we demonstrate that C/EBPβ LIP mediates epithelial growth factor (EGF)-induced EMT and increases migration and invasion of esophageal cancer cells in a manner that is dependent on miR-203 inactivation. Finally, we identified miR-203 as a direct target of C/EBPβ LIP. Disruption of C/EBPβ LIP attenuated the EGF-mediated decrease in miR-203, whereas overexpression of C/EBPβ LIP alone markedly suppressed miR-203. In addition, we demonstrated that C/EBPβ LIP inhibited miR-203 transcription by directly interacting with a conserved distal regulatory element upstream of the miR-203 locus, and in doing so, orchestrated chromatin remodeling. In conclusion, our results have revealed a new regulatory mechanism that involves C/EBPβ-LIP-mediated downregulation of miR-203, which plays a key role in EMT and metastasis.
authors.affiliation: Department of Medical Genetics, Third Military Medical University, Chongqing 400038, People's Republic of China.
authors.forename: Junxia
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pathophysiology and High Altitude Physiology, Third Military Medical University, Chongqing 400038, People's Republic of China.
authors.forename: Fabo
authors.initials: F
authors.lastname: Shan
authors.affiliation: Department of Thoracic and Cardiac Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, People's Republic of China.
authors.forename: Gang
authors.initials: G
authors.lastname: Xiong
authors.affiliation: Department of Medical Genetics, Third Military Medical University, Chongqing 400038, People's Republic of China.
authors.forename: Xuedan
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Medical Genetics, Third Military Medical University, Chongqing 400038, People's Republic of China.
authors.forename: Xingying
authors.initials: X
authors.lastname: Guan
authors.affiliation: Institute of Bioinformatics and Biosignal Transduction, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan 701, Taiwan.
authors.forename: Ju-Ming
authors.initials: JM
authors.lastname: Wang
authors.affiliation: Institute of Bioinformatics and Biosignal Transduction, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan 701, Taiwan.
authors.forename: Wen-Lin
authors.initials: WL
authors.lastname: Wang
authors.affiliation: Molecular Biology Center, State Key Laboratory of Trauma, Burn, and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing 400038, People's Republic of China buyi.chu@gmail.com baiy37@yahoo.com.cn.
authors.forename: Xueqing
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Medical Genetics, Third Military Medical University, Chongqing 400038, People's Republic of China buyi.chu@gmail.com baiy37@yahoo.com.cn.
authors.forename: Yun
authors.initials: Y
authors.lastname: Bai
mesh_terms: D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D004815:Epidermal Growth Factor / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics* / Q000502:physiology; D004938:Esophageal Neoplasms / Q000378:metabolism*; D000077277:Esophageal Squamous Cell Carcinoma; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; C546703:MIRN203 microRNA, human; D035683:MicroRNAs; D004815:Epidermal Growth Factor
keywords: C/EBPβ; ESCC; Epithelial–mesenchymal transition; Metastasis; miR-203