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Epithelial-Mesenchymal Transition (EMT): The Type-2 EMT in Wound Healing, Tissue Regeneration and Organ Fibrosis
Article

Snail Upregulates Transcription of FN, LEF, COX2, and COL1A1 in Hepatocellular Carcinoma: A General Model Established for Snail to Transactivate Mesenchymal Genes

1
Institute of Medical Sciences, Tzu Chi University, Hualien 970, Taiwan
2
Division of General Surgery, Department of Surgery, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan
3
Division of General Surgery, Department of Surgery, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and School of Medicine, Tzu Chi University, Hualien 970, Taiwan
4
Division of Gastroenterology, Department of Medicine, Research Centre for Hepatology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan
5
Department of Laboratory Medicine and Biotechnology, College of Medicine, Tzu Chi University, Hualien 970, Taiwan
6
Department of Molecular Biology and Human Genetics, Tzu Chi University, Hualien 970, Taiwan
*
Authors to whom correspondence should be addressed.
Academic Editors: Oriana Trubiani, Francesca Diomede, Jacopo Pizzicanella, Guya Diletta Marconi and Maurizio Onisto
Received: 17 July 2021 / Revised: 14 August 2021 / Accepted: 22 August 2021 / Published: 26 August 2021
(This article belongs to the Special Issue Latest Research on Epithelial-Mesenchymal Transition (EMT))
SNA is one of the essential EMT transcriptional factors capable of suppressing epithelial maker while upregulating mesenchymal markers. However, the mechanisms for SNA to transactivate mesenchymal markers was not well elucidated. Recently, we demonstrated that SNA collaborates with EGR1 and SP1 to directly upregulate MMP9 and ZEB1. Remarkably, a SNA-binding motif (TCACA) upstream of EGR/SP1 overlapping region on promoters was identified. Herein, we examined whether four other mesenchymal markers, lymphoid enhancer-binding factor (LEF), fibronectin (FN), cyclooxygenase 2 (COX2), and collagen type alpha I (COL1A1) are upregulated by SNA in a similar fashion. Expectedly, SNA is essential for expression of these mesenchymal genes. By deletion mapping and site directed mutagenesis coupled with dual luciferase promoter assay, SNA-binding motif and EGR1/SP1 overlapping region are required for TPA-induced transcription of LEF, FN, COX2 and COL1A1. Consistently, TPA induced binding of SNA and EGR1/SP1 on relevant promoter regions of these mesenchymal genes using ChIP and EMSA. Thus far, we found six of the mesenchymal genes are transcriptionally upregulated by SNA in the same fashion. Moreover, comprehensive screening revealed similar sequence architectures on promoter regions of other SNA-upregulated mesenchymal markers, suggesting that a general model for SNA-upregulated mesenchymal genes can be established. View Full-Text
Keywords: snail; fibronectin; lymphoid enhancer-binding factor; cyclooxygenase 2; collagen type alpha I; transcription snail; fibronectin; lymphoid enhancer-binding factor; cyclooxygenase 2; collagen type alpha I; transcription
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MDPI and ACS Style

Ly, T.M.; Chen, Y.-C.; Lee, M.-C.; Hu, C.-T.; Cheng, C.-C.; Chang, H.-H.; You, R.-I.; Wu, W.-S. Snail Upregulates Transcription of FN, LEF, COX2, and COL1A1 in Hepatocellular Carcinoma: A General Model Established for Snail to Transactivate Mesenchymal Genes. Cells 2021, 10, 2202. https://0-doi-org.brum.beds.ac.uk/10.3390/cells10092202

AMA Style

Ly TM, Chen Y-C, Lee M-C, Hu C-T, Cheng C-C, Chang H-H, You R-I, Wu W-S. Snail Upregulates Transcription of FN, LEF, COX2, and COL1A1 in Hepatocellular Carcinoma: A General Model Established for Snail to Transactivate Mesenchymal Genes. Cells. 2021; 10(9):2202. https://0-doi-org.brum.beds.ac.uk/10.3390/cells10092202

Chicago/Turabian Style

Ly, Tam M., Yen-Cheng Chen, Ming-Che Lee, Chi-Tan Hu, Chuan-Chu Cheng, Hsin-Hou Chang, Ren-In You, and Wen-Sheng Wu. 2021. "Snail Upregulates Transcription of FN, LEF, COX2, and COL1A1 in Hepatocellular Carcinoma: A General Model Established for Snail to Transactivate Mesenchymal Genes" Cells 10, no. 9: 2202. https://0-doi-org.brum.beds.ac.uk/10.3390/cells10092202

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