Abstract
ABSTRACT MarvelD3, a recently identified tight junction membrane protein, could be associated with hepatocellular carcinoma (HCC). We aimed to investigate the role of marvelD3 in Epithelial–Mesenchymal Transition (EMT) and migration of HCC and explore the underlying molecular mechanisms. First, we assessed marvlD3 expression in HCC and normal liver tissues and found loss of marvelD3 expression was significantly correlated with the occurrence and TNM stage of HCC. Second, we detected that marvelD3 was downregulated in HCC cells with transforming growth factor β1 and snail/slug-induced EMT. Finally, we analyzed expression of marvelD3 protein was significantly associated with EMT and the NF-κB signaling pathway. Our study demonstrated that MarvelD3 inhibited EMT and migration of HCC cells along with inhibiting NF-κB signaling pathway. Abbreviations: HCC, Hepatocellular carcinoma; TJ, Tight junction; MARVEL, MAL and related proteins for vesicle trafficking and membrane link; EMT, Epithelial–mesenchymal transition; NF-κB, Nuclear factor kappa B; TAMPs, Tight junction-associated marvel proteins; TGF-β1, Transforming growth factor-β1; MMP9, matrix metallopeptidase 9; RT-PCR, Real-time PCR; IHC, Immunohistochemistry; IF, Immunofluorescence.
Highlights
Tight junctions (TJs), which are an intercellular adhesion complex of epithelial and endothelial cells, are very important for the growth of metastatic cancer cells
We aimed to demonstrate the role of marvelD3 in inhibiting hepatocellular carcinoma (HCC) epithelial–mesenchymal transition (EMT) and migration and further explore the underlying molecular mechanisms
Loss of marvelD3 expression was significantly correlated with the occurrence and TNM stage of HCC
Summary
Tight junctions (TJs), which are an intercellular adhesion complex of epithelial and endothelial cells, are very important for the growth of metastatic cancer cells. TJs consist of tight junction-associated marvel proteins (TAMPs) (occludin, tricellulin, and marvelD3) and claudins. Claudins regulate the interactions between occludin, tricellulin, and marvelD3, which inversely modulate claudin oligomerization [2]. Their cross-linking functions have been associated with the regulation of signal transduction mechanisms that lead to epithelial cell proliferation and differentiation [4]. MarvelD3, which contains a conserved MARVEL (MAL and related proteins for vesicle trafficking and membrane link) domain to occludin and tricellulin, is a recently identified integral membrane protein that forms TJs. little is known about the possible roles of marvelD3 in epithelial–mesenchymal transition (EMT) and metastasis of HCC. We aimed to demonstrate the role of marvelD3 in inhibiting HCC EMT and migration and further explore the underlying molecular mechanisms
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