Abstract
MUC4 is a predominant membrane-tethered mucin lubricating and protecting the epithelial surface and playing various biological roles in the renewal and differentiation of epithelial cells, cell signaling, cell adhesion, and carcinogenesis. Interestingly, recent studies have demonstrated that MUC4 expression regulates the epithelial-mesenchymal transition (EMT) of cancer cells in ovarian, pancreatic, and lung cancer. However, the effects of MUC4 expression on EMT in human airway epithelial cells are not yet well known. Here, we describe the effects of transforming growth factor beta 1 (TGF-β1)-induced MUC4 expression on EMT and evaluate its downstream signaling pathway in human airway epithelial cells. In human airway epithelial NCI-H292 cells, exposure to TGF-β1 induced expression of MUC4, CDH2, VIM and SNAI1 genes and encoded by them proteins, MUC4, N-cadherin, vimentin and Snail, and reduced the level of CDH1 and its product, E-cadherin. In MUC4-knockdown cells, TGF-β1-induced expression levels of MUC4, CDH2, VIM and SNAI1 and corresponding proteins were suppressed, but CDH1 and E-cadherin levels were not. In addition, TGF-β1-induced phosphorylation of extracellular signal regulated kinase 1/2 (ERK1/2) was suppressed, but that of Smad2/3, Akt, and p38 was not. The results of this study suggest that MUC4 silencing inhibits TGF-β1-induced EMT via the ERK1/2 pathway, and a possible role of MUC4 in the induction of EMT in human airway epithelial cells.
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This study was supported by the 2017 Yeungnam University Research Grant.
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The authors declare they have no conflict of interest.
This article does not contain any studies involving animals or human participants performed by any of the authors. All experimental protocols were approved by the Yeungnam University Hospital-Institutional Review Board (file no. 2018-08-011).
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Kim, YD., Choi, Y.S., Na, H.G. et al. MUC4 Silencing Inhibits TGF-β1-Induced Epithelial-Mesenchymal Transition via the ERK1/2 Pathway in Human Airway Epithelial NCI-H292 Cells. Mol Biol 55, 565–572 (2021). https://doi.org/10.1134/S0026893321030079
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DOI: https://doi.org/10.1134/S0026893321030079