Knockdown of 14-kDa phosphohistidine phosphatase expression suppresses lung cancer cell growth in vivo possibly through inhibition of NF-κB signaling pathway.
In previous study, we reported that 14-kDa phosphohistidine phosphatase (PHP14) was associated with lung cancer cell migration and invasion. We also found that the expression of PHP14 was markedly increased in a part of human lung cancer tissues. In this study, we investigated the impact of PHP14 knockdown on lung cancer cell tumorigenesis in vitro and in vivo, as well as the regulatory pathway. Depletion of endogenous PHP14 expression in lung cancer cells reduced colony formation activity of lung cancer cells in vitro and inhibited the xenograft tumor growth in vivo. Further experiments revealed that the NF-κB signal pathway inhibitor PDTC inhibited the upregulated expression of MMP9 induced by PHP14 overexpression in lung cancer cells. Furthermore, knockdown of PHP14 in lung cancer cells correlated with decreased expression of a subset of NF-κB-regulated genes, such as BCL-2, COX-2, MCP-1, MMP9 and VEGF-C, which play an important role in tumor progression. Together these data suggest that knockdown of PHP14 in lung cancer cells inhibits lung cancer tumor growth in vivo, possibly via regulating the NF-κB pathway.
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Xu
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Li
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Wu
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Lv
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Jin
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Sun
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Huang
D002465:Cell Movement / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D055785:Gene Knockdown Techniques; D006639:Histidine / Q000031:analogs & derivatives; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics; D015398:Signal Transduction
D016328:NF-kappa B; D006639:Histidine; D010744:Phosphoric Monoester Hydrolases; D020780:Matrix Metalloproteinase 9; C005436:phosphohistidine
14-kDa phosphohistidine phosphatase; NF-κB signaling pathway; RNA interference.; lung cancer