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PADI4 promotes epithelial-mesenchymal transition(EMT) in gastric cancer via the upregulation of interleukin 8
BACKGROUND: Gastric cancer (GC) is one of the deadliest tumours due to its ability to metastasize. The Epithelial–to-mesenchymal transition plays a crucial role in promoting the GC metastasis, which increases the migration and metastasis of tumour cells. Peptidyl arginine deiminase IV (PADI4) is a s...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8767667/ https://www.ncbi.nlm.nih.gov/pubmed/35045833 http://dx.doi.org/10.1186/s12876-022-02097-0 |
Sumario: | BACKGROUND: Gastric cancer (GC) is one of the deadliest tumours due to its ability to metastasize. The Epithelial–to-mesenchymal transition plays a crucial role in promoting the GC metastasis, which increases the migration and metastasis of tumour cells. Peptidyl arginine deiminase IV (PADI4) is a susceptibility gene for gastric carcinoma. The aim of this study was to evaluate the functional roles of PADI4 in gastric cancer. METHODS: The expression of PADI4 was examined by qRT-PCR, western blot and immunohistochemistry. In addition, the functional roles of PADI4 were explored by over-expression PADI4 plasmids in gastric cancer cells. RESULTS: We found that the expression of PADI4 was up-regulated in GC. PADI4 overexpression in GC cells increased the proliferation, migration, metastasis, clone forming ability, and tumorigenic ability, but reduced the apoptosis ability. The Multi-Analyte ELISArray Kit results showed that interleukin 8 (IL-8) is upregulated in PADI4-overexpressing gastric cells. Using short interfering RNA (siRNA) to silence the expression of IL-8, we demonstrated that IL-8 silencing significantly inhibited the increased migratory capacity in PADI4-overexpressing GC cells. CONCLUSIONS: Our data suggest that PADI4 accelerate metastasis by promoting IL-8 expression in gastric cancer cells, indicating that it is a new PADI4/IL-8 signalling pathway in metastatic GC. |
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