EGF-induced C/EBPβ participates in EMT by decreasing the expression of miR-203 in esophageal squamous cell carcinoma cells

Junxia Li, Fabo Shan, Gang Xiong, Xuedan Chen, Xingying Guan, Ju-Ming Wang, Wen Lin Wang, Xueqing Xu, Yun Bai

研究成果: Article

14 引文 (Scopus)

摘要

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/EBPb 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.

原文English
頁(從 - 到)3735-3744
頁數10
期刊Journal of Cell Science
127
發行號17
DOIs
出版狀態Published - 2014 一月 1

指紋

CCAAT-Enhancer-Binding Proteins
Epithelial-Mesenchymal Transition
Intercellular Signaling Peptides and Proteins
Neoplasm Metastasis
Chromatin Assembly and Disassembly
Esophageal Neoplasms
Esophageal Squamous Cell Carcinoma
Neoplasms
Protein Isoforms
Down-Regulation

All Science Journal Classification (ASJC) codes

  • Cell Biology

引用此文

Li, Junxia ; Shan, Fabo ; Xiong, Gang ; Chen, Xuedan ; Guan, Xingying ; Wang, Ju-Ming ; Wang, Wen Lin ; Xu, Xueqing ; Bai, Yun. / EGF-induced C/EBPβ participates in EMT by decreasing the expression of miR-203 in esophageal squamous cell carcinoma cells. 於: Journal of Cell Science. 2014 ; 卷 127, 編號 17. 頁 3735-3744.
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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/EBPb 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.",
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EGF-induced C/EBPβ participates in EMT by decreasing the expression of miR-203 in esophageal squamous cell carcinoma cells. / Li, Junxia; Shan, Fabo; Xiong, Gang; Chen, Xuedan; Guan, Xingying; Wang, Ju-Ming; Wang, Wen Lin; Xu, Xueqing; Bai, Yun.

於: Journal of Cell Science, 卷 127, 編號 17, 01.01.2014, p. 3735-3744.

研究成果: Article

TY - JOUR

T1 - EGF-induced C/EBPβ participates in EMT by decreasing the expression of miR-203 in esophageal squamous cell carcinoma cells

AU - Li, Junxia

AU - Shan, Fabo

AU - Xiong, Gang

AU - Chen, Xuedan

AU - Guan, Xingying

AU - Wang, Ju-Ming

AU - Wang, Wen Lin

AU - Xu, Xueqing

AU - Bai, Yun

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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/EBPb 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.

AB - 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/EBPb 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.

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