- 作者: Chi-Shu Sun; Kuan-Ta Wu; Hao-Hsien Lee; Yih-Huei Uen; Yu-Feng Tian; Cheng-Chen Tzeng; Andrew H.-J. Wang; Chia-Ju Cheng; Sun-Lung Tsai
- 作者服務機構: Division of Hepatogastroenterology,Department of Internal Medicine,Chi Mei Medical Center, Tainan, Taiwan; Division of General Surgery,Department of Surgery,Chi Mei Hospital Liouying, Tainan, Taiwan; Division of General Surgery,Department of Surgery,Chi Mei Medical Center, Tainan, Taiwan
- 中文摘要: --
- 英文摘要: The link of proto-oncogenic protein Wnt-1production with NF-jB activation has been functionallydemonstrated in PC12 cells, a rat pheochromocytoma cellline of neural crest lineage, while it is not yet verified inhuman cells. The link can be indirectly supported in ourprevious report that functional proteomics identifiesenhanced expression of NF-jB-associated Wnt-1production in human hepatocellular carcinoma tissues. Thisstudy aimed to further validate this link in human cellsusing anti-sense strategy. The effects of sequence-specificanti-sense morpholino oligonucleotides (ONs) targetingagainst pre-mRNA sequences of human p50 and p65 subunitsof NF-jB as well as Wnt-1 genes were investigated. Itrevealed that all the three morpholino ONs inhibited NFjBactivation in human hepatoblastoma cell line HepG2cells along with decreased Wnt-1 production. Chromatinimmunoprecipitation assay ascertained the direct bindingof NF-jB-p50 to the Wnt-1 promoter. Additionally, anti-P50 and anti-P65 morpholino ONs also repressed thephosphorylation of Ij Ba which temporarily correlatedwith the inhibition of NF-jB activation accompanied bydecreased Wnt-1 production by HepG2 cells. In summary,NF-jB activation is critically involved in the production ofWnt-1 by HepG2 cells. These results may have importantoncology implications in treating patients with NF-jBassociatedWnt-1-producing cancers.
- 中文關鍵字: --
- 英文關鍵字: Anti-sense strategy; Chromatinimmunoprecipitation assay; HepG2 cells; Ij B; Morpholino oligonucleotide; NF-jB; Wnt-1 protein