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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

  • Authors:
    • Yuki Miyake
    • Yoshiyuki Nagaoka
    • Kazuhiko Okamura
    • Yukimasa Takeishi
    • Sachio Tamaoki
    • Mitsutoki Hatta
  • View Affiliations / Copyright

    Affiliations: Department of Physiological Science and Molecular Biology, Fukuoka Dental College, Fukuoka 814‑0193, Japan, Department of Morphological Biology, Fukuoka Dental College, Fukuoka 814‑0193, Japan, Department of Oral Growth and Development, Fukuoka Dental College, Fukuoka 814‑0193, Japan
    Copyright: © Miyake et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 1124
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    Published online on: August 4, 2021
       https://doi.org/10.3892/etm.2021.10558
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Abstract

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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Copy and paste a formatted citation
Spandidos Publications style
Miyake Y, Nagaoka Y, Okamura K, Takeishi Y, Tamaoki S and Hatta M: SNAI2 is induced by transforming growth factor‑β1, but is not essential for epithelial‑mesenchymal transition in human keratinocyte HaCaT cells. Exp Ther Med 22: 1124, 2021.
APA
Miyake, Y., Nagaoka, Y., Okamura, K., Takeishi, Y., Tamaoki, S., & Hatta, M. (2021). SNAI2 is induced by transforming growth factor‑β1, but is not essential for epithelial‑mesenchymal transition in human keratinocyte HaCaT cells. Experimental and Therapeutic Medicine, 22, 1124. https://doi.org/10.3892/etm.2021.10558
MLA
Miyake, Y., Nagaoka, Y., Okamura, K., Takeishi, Y., Tamaoki, S., Hatta, M."SNAI2 is induced by transforming growth factor‑β1, but is not essential for epithelial‑mesenchymal transition in human keratinocyte HaCaT cells". Experimental and Therapeutic Medicine 22.4 (2021): 1124.
Chicago
Miyake, Y., Nagaoka, Y., Okamura, K., Takeishi, Y., Tamaoki, S., Hatta, M."SNAI2 is induced by transforming growth factor‑β1, but is not essential for epithelial‑mesenchymal transition in human keratinocyte HaCaT cells". Experimental and Therapeutic Medicine 22, no. 4 (2021): 1124. https://doi.org/10.3892/etm.2021.10558
Copy and paste a formatted citation
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Spandidos Publications style
Miyake Y, Nagaoka Y, Okamura K, Takeishi Y, Tamaoki S and Hatta M: SNAI2 is induced by transforming growth factor‑β1, but is not essential for epithelial‑mesenchymal transition in human keratinocyte HaCaT cells. Exp Ther Med 22: 1124, 2021.
APA
Miyake, Y., Nagaoka, Y., Okamura, K., Takeishi, Y., Tamaoki, S., & Hatta, M. (2021). SNAI2 is induced by transforming growth factor‑β1, but is not essential for epithelial‑mesenchymal transition in human keratinocyte HaCaT cells. Experimental and Therapeutic Medicine, 22, 1124. https://doi.org/10.3892/etm.2021.10558
MLA
Miyake, Y., Nagaoka, Y., Okamura, K., Takeishi, Y., Tamaoki, S., Hatta, M."SNAI2 is induced by transforming growth factor‑β1, but is not essential for epithelial‑mesenchymal transition in human keratinocyte HaCaT cells". Experimental and Therapeutic Medicine 22.4 (2021): 1124.
Chicago
Miyake, Y., Nagaoka, Y., Okamura, K., Takeishi, Y., Tamaoki, S., Hatta, M."SNAI2 is induced by transforming growth factor‑β1, but is not essential for epithelial‑mesenchymal transition in human keratinocyte HaCaT cells". Experimental and Therapeutic Medicine 22, no. 4 (2021): 1124. https://doi.org/10.3892/etm.2021.10558
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