Alpha-fetoprotein producing gastric cancer cells lack transcription factor AT-motif binding factor 1 (ATBF1)

Abstract Background Glutathione Peroxidase 8 (GPX8) as a member of the glutathione peroxidase (GPx) family plays an important role in anti-oxidation. Besides, dysregulation of GPX8 has been found in gastric cancer, but its detailed molecular mechanism in gastric cancer has not been reported. Methods Our study detected the expression of GPX8 in gastric cancer tissues and cell lines using immunohistochemistry (IHC), western blot and qRT-PCR, and determined the effect of GPX8 on gastric cancer cells using CCK-8, colony formation, transwell migration and invasion assays. Besides, the effect of GPX8 on the Wnt signaling pathway was determined by western blot. Furthermore, the transcription factor of GPX8 was identified by bioinformatics methods, dual luciferase reporter and chromatin immunoprecipitation (CHIP) assays. In addition, the effect of GPX8 on tumor formation was measured by IHC and western blot. Results The over-expression of GPX8 was observed in gastric cancer tissues and cells, which facilitated the proliferation, migration and invasion of gastric cancer cells as well as the tumor growth. GPX8 knockdown effectively inhibited the growth of gastric cancer cells and tumors. Moreover, GPX8 could activate the Wnt signaling pathway to promote the cellular proliferation, migration and invasion through. Furthermore, FOXC1 was identified as a transcription factor of GPX8 and mediated GPX8 expression to affect cell development processes. Conclusions These findings contribute to understanding the molecular mechanism of GPX8 in gastric cancer. Additionally, GPX8 can be a potential biomarker for gastric cancer therapy.

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Constitutive phosphorylation of the FOXO1 transcription factor in gastric cancer cells correlates with microvessel area and the expressions of angiogenesis-related molecules

BMC Cancer ◽

10.1186/1471-2407-11-264 ◽

2011 ◽

Vol 11 (1) ◽

Cited By ~ 29

Author(s):

Sue Youn Kim ◽

Jiyeon Yoon ◽

Young San Ko ◽

Mee Soo Chang ◽

Jong-Wan Park ◽

...

Keyword(s):

Gastric Cancer ◽

Transcription Factor ◽

Cancer Cells ◽

Gastric Cancer Cells ◽

Constitutive Phosphorylation

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Activating Transcription Factor 4 Confers a Multidrug Resistance Phenotype to Gastric Cancer Cells through Transactivation of SIRT1 Expression

PLoS ONE ◽

10.1371/journal.pone.0031431 ◽

2012 ◽

Vol 7 (2) ◽

pp. e31431 ◽

Cited By ~ 31

Author(s):

Hongwu Zhu ◽

Limin Xia ◽

Yongguo Zhang ◽

Honghong Wang ◽

Wenjing Xu ◽

...

Keyword(s):

Gastric Cancer ◽

Transcription Factor ◽

Multidrug Resistance ◽

Cancer Cells ◽

Gastric Cancer Cells ◽

Resistance Phenotype ◽

Sirt1 Expression ◽

Activating Transcription Factor 4 ◽

Activating Transcription Factor ◽

Transcription Factor 4

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Inhibition of migration and invasion of gastric cancer cells by Snail-regulated MiR-375 through JAK2 targeting.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.3_suppl.56 ◽

2014 ◽

Vol 32 (3_suppl) ◽

pp. 56-56

Author(s):

Xu Yanjun ◽

Zhou Tianhua ◽

Si Jianmin ◽

Zhuo Wei

Keyword(s):

Gastric Cancer ◽

Transcription Factor ◽

Cancer Cells ◽

Expression Level ◽

Luciferase Assay ◽

Surrounding Tissue ◽

Migration And Invasion ◽

Pcr Analysis ◽

Invasion And Metastasis ◽

Gastric Cancer Cells

56 Background: Migration and invasion of cancer cells are essential process during cancer metastatic procession. In gastric cancer, cells invasion into the surrounding tissue is a crucial early step. However, the mechanisms have not been fully understood. MicroRNAs, which are a class of small single-stranded non-coding RNA, participate in the malignant progressions of cancer, including metastasis. We study the association between specific dysregulated miRNA and specific metastasis step of gastric cancer, which will provide insights into the potential mechanisms of gastric cancer cells migration, invasion and metastasis. Methods: The expression of miR-375 was assayed using the quantitative real-time PCR analysis. Scratch-wound healing assay, Transwell migration and invasion assay were conducted to study the migration and invasion abilities of cells. Animal experiment was also conducted to examine the effect on liver and lung metastases by overexpression of miR-375. Luciferase assay was conducted to study the association between Snail and miR-375. Results: MiR-375 is downregulated in gastric cancer cells with greater migration and invasion abilities. The expression level of miR-375 is decreased in gastric cancer tissues from metastasis-positive patients compared with that from metastasis-free patients. Overexpression of miR-375 inhibits the migration and invasion abilities of gastric cancer cells. JAK2, which may be a target gene of miR-375, could reverses miR-375 induced inhibition of gastric cancer cells migration and invasion. Liver metastasis was not detected in mice injected with miR-375 overexpressed cells but was apparent in mice injected with cells which were transfected with control vector. The transcription factor Snail, which binds directly to the putative promoter of miR-375, could reduce the expression level of miR-375 significantly. A distinct inverse correlation was found between miR-375 expression and Snail mRNA level. Conclusions: These findings demonstrate that tumor suppressor miR-375, whose expression is directly regulated by the transcription factor Snail, inhibits gastric cancer cells migration, invasion and metastasis by targeting an important protein JAK2.

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