Study on the role of POU3F2 in cancer cell apoptosis
| Autor: | Chun-Yung Huang, 黃俊詠 |
|---|---|
| Rok vydání: | 2019 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 107 Taiwan is one of the regions with high prevalence of gastric cancer. However, the pathogenesis of gastric cancer is extremely complicated and has not been thoroughly studied. POU3F2 is a POU-homeodomain transcription factor, and is thought to play important roles in neuronal differentiation, melanocyte growth, differentiation and tumorigenesis. However, the function of POU3F2 in gastric cancer has not been well studied. We apply the bioinformatics tools to predict the transcriptional target genes of POU3F2, and found that POU3F2 may regulate several apoptosis genes including GADD45A. Here, we report that overexpression of POU3F2 increase apoptosis in gastric cancer AGS cells by Flow Cytometry. The RNA and protein level of the known POU3F2 transcriptional target gene GADD45A are increased by the overexpression of POU3F2, and lead to the activation of the downstream protein p38. In addition, in POU3F2-overexpressed AGS cells, increase of the phosphorylated p53, APAF-1 expression, PARP cleavage, and downregulation of the anti-apoptotic protein Bcl-2 appeared to be associated with the increase in apoptosis response, and vice versa. Furthermore, both p53 knockdown and p38 inhibiton can prevent the apoptosis induced by overexpression of POU3F2. And the overexpression of POU3F2 in gastric cancer KATO III cells (p53-null) can increase the expression of GADD45A and the phosphorylation of p38, but cannot promote apoptosis. We also found UVB radiation and alkylating agent will increase POU3F2 expression and promote the following apoptosis pathway through GADD45A─p38─p53 axis. Taken together, our results provide the first evidence for a molecular mechanism of POU3F2 acts through GADD45A─p38─p53 axis to induce apoptosis in gastric cancer cells. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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