Claudin 1 mediates tumor necrosis factor alpha-induced cell migration in human gastric cancer cells
| Autor: | Yoshito Nako, Takeshi Kubota, Kazuma Okamoto, Eigo Otsuji, Shuhei Komatsu, Hitoshi Fujiwara, Mingyao Liu, Hiroki Shimizu, Daisuke Ichikawa, Hirotaka Konishi, Daisuke Iitaka, Shingo Nakashima, Atsushi Shiozaki |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Small interfering RNA
Apoptosis Adenocarcinoma Biology Real-Time Polymerase Chain Reaction Transfection Cell Movement Stomach Neoplasms Cell Line Tumor Claudin-1 Humans Neoplasm Invasiveness RNA Messenger Claudin Cell Proliferation Oligonucleotide Array Sequence Analysis Gene knockdown Tumor Necrosis Factor-alpha Microarray analysis techniques Gene Expression Profiling Gastroenterology Computational Biology Cell migration Cell Cycle Checkpoints General Medicine Cell cycle digestive system diseases Up-Regulation Gene Expression Regulation Neoplastic Cancer cell Immunology Cancer research Original Article RNA Interference Signal Transduction |
| Zdroj: | World Journal of Gastroenterology. 20:17863-17876 |
| ISSN: | 1007-9327 |
| DOI: | 10.3748/wjg.v20.i47.17863 |
| Popis: | AIM: To investigate the role of claudin 1 in the regulation of genes involved in cell migration and tumor necrosis factor alpha (TNF-α)-induced gene expression in human gastric adenocarcinoma cells. METHODS: Knockdown experiments were conducted with claudin 1 small interfering RNA (siRNA), and the effects on the cell cycle, apoptosis, migration and invasion were analyzed in human gastric adenocarcinoma MKN28 cells. The gene expression profiles of cells were analyzed by microarray and bioinformatics. RESULTS: The knockdown of claudin 1 significantly inhibited cell proliferation, migration and invasion, and increased apoptosis. Microarray analysis identified 245 genes whose expression levels were altered by the knockdown of claudin 1. Pathway analysis showed that the top-ranked molecular and cellular function was the cellular movement related pathway, which involved MMP7, TNF-SF10, TGFBR1, and CCL2. Furthermore, TNF- and nuclear frctor-κB were the top-ranked upstream regulators related to claudin 1. TNF-α treatment increased claudin 1 expression and cell migration in MKN28 cells. Microarray analysis indicated that the depletion of claudin 1 inhibited 80% of the TNF-α-induced mRNA expression changes. Further, TNF-α did not enhance cell migration in the claudin 1 siRNA transfected cells. CONCLUSION: These results suggest that claudin 1 is an important messenger that regulates TNF-α-induced gene expression and migration in gastric cancer cells. A deeper understanding of these cellular processes may be helpful in establishing new therapeutic strategies for gastric cancer. |
| Databáze: | OpenAIRE |
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