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SNAI2 is induced by transforming growth factor-β1, but is not essential for epithelial-mesenchymal transition in human keratinocyte HaCaT cells

Epithelial-mesenchymal transition (EMT) is a cellular process in which epithelial cells lose their epithelial traits and shift to the mesenchymal phenotype, and is associated with various biological events, such as embryogenesis, wound healing and cancer progression. The transcriptional program that...

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Autores principales: Miyake, Yuki, Nagaoka, Yoshiyuki, Okamura, Kazuhiko, Takeishi, Yukimasa, Tamaoki, Sachio, Hatta, Mitsutoki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8383325/
https://www.ncbi.nlm.nih.gov/pubmed/34466140
http://dx.doi.org/10.3892/etm.2021.10558
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author Miyake, Yuki
Nagaoka, Yoshiyuki
Okamura, Kazuhiko
Takeishi, Yukimasa
Tamaoki, Sachio
Hatta, Mitsutoki
author_facet Miyake, Yuki
Nagaoka, Yoshiyuki
Okamura, Kazuhiko
Takeishi, Yukimasa
Tamaoki, Sachio
Hatta, Mitsutoki
author_sort Miyake, Yuki
collection PubMed
description Epithelial-mesenchymal transition (EMT) is a cellular process in which epithelial cells lose their epithelial traits and shift to the mesenchymal phenotype, and is associated with various biological events, such as embryogenesis, wound healing and cancer progression. The transcriptional program that promotes phenotype switching is dynamically controlled by transcription factors during EMT, including Snail (SNAI1), twist family bHLH transcription factor (TWIST) and zinc finger E-box binding homeobox 1 (ZEB1). The present study aimed to investigate the molecular mechanisms underlying EMT in squamous epithelial cells. Western blot analysis and immunocytochemical staining identified Slug (SNAI2) as a transcription factor that is induced during transforming growth factor (TGF)-β1-mediated EMT in the human keratinocyte cell line HaCaT. The effect of SNAI2 overexpression and knockdown on the phenotypic characteristics of HaCaT cells was evaluated. Filamentous actin staining and western blot analysis revealed that the overexpression of SNAI2 did not induce the observed EMT-related phenotypic changes. In addition, SNAI2 knockdown demonstrated almost no impact on the EMT phenotypes induced by TGF-β1. Notably, DNA microarray analysis followed by comprehensive bioinformatics analysis revealed that the differentially expressed genes upregulated by TGF-β1 were significantly enriched in cell adhesion and extracellular matrix binding, whereas the genes downregulated in response to TGF-β1 were significantly enriched in the cell cycle. No enriched gene ontology term and biological pathways were identified in the differentially expressed gene sets of SNAI2-overexpressing cells. In addition, the candidates for master transcription factors regulating the TGF-β1-induced EMT were identified using transcription factor enrichment analysis. In conclusion, the results of study demonstrated that SNAI2 does not play an essential role in the EMT of HaCaT cells and identified candidate transcription factors that may be involved in EMT-related gene expression induced by TGF-β1. These findings may enhance the understanding of molecular events in EMT and contribute to the development of a novel therapeutic approach against EMT in cancers and wound healing.
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spelling pubmed-83833252021-08-30 SNAI2 is induced by transforming growth factor-β1, but is not essential for epithelial-mesenchymal transition in human keratinocyte HaCaT cells Miyake, Yuki Nagaoka, Yoshiyuki Okamura, Kazuhiko Takeishi, Yukimasa Tamaoki, Sachio Hatta, Mitsutoki Exp Ther Med Articles Epithelial-mesenchymal transition (EMT) is a cellular process in which epithelial cells lose their epithelial traits and shift to the mesenchymal phenotype, and is associated with various biological events, such as embryogenesis, wound healing and cancer progression. The transcriptional program that promotes phenotype switching is dynamically controlled by transcription factors during EMT, including Snail (SNAI1), twist family bHLH transcription factor (TWIST) and zinc finger E-box binding homeobox 1 (ZEB1). The present study aimed to investigate the molecular mechanisms underlying EMT in squamous epithelial cells. Western blot analysis and immunocytochemical staining identified Slug (SNAI2) as a transcription factor that is induced during transforming growth factor (TGF)-β1-mediated EMT in the human keratinocyte cell line HaCaT. The effect of SNAI2 overexpression and knockdown on the phenotypic characteristics of HaCaT cells was evaluated. Filamentous actin staining and western blot analysis revealed that the overexpression of SNAI2 did not induce the observed EMT-related phenotypic changes. In addition, SNAI2 knockdown demonstrated almost no impact on the EMT phenotypes induced by TGF-β1. Notably, DNA microarray analysis followed by comprehensive bioinformatics analysis revealed that the differentially expressed genes upregulated by TGF-β1 were significantly enriched in cell adhesion and extracellular matrix binding, whereas the genes downregulated in response to TGF-β1 were significantly enriched in the cell cycle. No enriched gene ontology term and biological pathways were identified in the differentially expressed gene sets of SNAI2-overexpressing cells. In addition, the candidates for master transcription factors regulating the TGF-β1-induced EMT were identified using transcription factor enrichment analysis. In conclusion, the results of study demonstrated that SNAI2 does not play an essential role in the EMT of HaCaT cells and identified candidate transcription factors that may be involved in EMT-related gene expression induced by TGF-β1. These findings may enhance the understanding of molecular events in EMT and contribute to the development of a novel therapeutic approach against EMT in cancers and wound healing. D.A. Spandidos 2021-10 2021-08-04 /pmc/articles/PMC8383325/ /pubmed/34466140 http://dx.doi.org/10.3892/etm.2021.10558 Text en Copyright: © Miyake et al. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Miyake, Yuki
Nagaoka, Yoshiyuki
Okamura, Kazuhiko
Takeishi, Yukimasa
Tamaoki, Sachio
Hatta, Mitsutoki
SNAI2 is induced by transforming growth factor-β1, but is not essential for epithelial-mesenchymal transition in human keratinocyte HaCaT cells
title SNAI2 is induced by transforming growth factor-β1, but is not essential for epithelial-mesenchymal transition in human keratinocyte HaCaT cells
title_full SNAI2 is induced by transforming growth factor-β1, but is not essential for epithelial-mesenchymal transition in human keratinocyte HaCaT cells
title_fullStr SNAI2 is induced by transforming growth factor-β1, but is not essential for epithelial-mesenchymal transition in human keratinocyte HaCaT cells
title_full_unstemmed SNAI2 is induced by transforming growth factor-β1, but is not essential for epithelial-mesenchymal transition in human keratinocyte HaCaT cells
title_short SNAI2 is induced by transforming growth factor-β1, but is not essential for epithelial-mesenchymal transition in human keratinocyte HaCaT cells
title_sort snai2 is induced by transforming growth factor-β1, but is not essential for epithelial-mesenchymal transition in human keratinocyte hacat cells
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8383325/
https://www.ncbi.nlm.nih.gov/pubmed/34466140
http://dx.doi.org/10.3892/etm.2021.10558
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