TY - JOUR
T1 - Snail upregulates transcription of fn, lef, cox2, and col1a1 in hepatocellular carcinoma
T2 - A general model established for snail to transactivate mesenchymal genes
AU - Ly, Tam Minh
AU - Chen, Yen Cheng
AU - Lee, Ming Che
AU - Hu, Chi Tan
AU - Chen, Chuan Chu
AU - Chang, Hsin Hou
AU - You, Ren In
AU - Wu, Wen Sheng
N1 - Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/9
Y1 - 2021/9
N2 - SNA is one of the essential EMT transcriptional factors capable of suppressing epithelial maker while upregulating mesenchymal markers. However, the mechanisms for SNA to transacti-vate 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 exam-ined whether four other mesenchymal markers, lymphoid enhancer-binding factor (LEF), fibron-ectin (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 mesen-chymal genes can be established.
AB - SNA is one of the essential EMT transcriptional factors capable of suppressing epithelial maker while upregulating mesenchymal markers. However, the mechanisms for SNA to transacti-vate 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 exam-ined whether four other mesenchymal markers, lymphoid enhancer-binding factor (LEF), fibron-ectin (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 mesen-chymal genes can be established.
KW - Collagen type alpha I
KW - Cyclooxygenase 2
KW - Fibronectin
KW - Lymphoid enhancer-binding factor
KW - Snail
KW - Transcription
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U2 - 10.3390/cells10092202
DO - 10.3390/cells10092202
M3 - Article
C2 - 34571852
AN - SCOPUS:85115901099
SN - 2073-4409
VL - 10
JO - Cells
JF - Cells
IS - 9
M1 - 2202
ER -