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纤维粘连蛋白EDA片段抑制P53核转位调控肠癌SW480细胞凋亡
Fibronectin extra domain A suppresses apoptosis of colorectal cancer SW480 cells by inhibiting P53 nuclear translocation
- 第三军医大学学报 2017年39卷第8期 页码：787-793
- 作者机构：
- 作者简介：
- 基金信息：
DOI：10.16016/j.1000-5404.201610068
中图分类号：-
纸质出版：2017-04
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杨卫文, 张月, 谢雄, 等. 纤维粘连蛋白EDA片段抑制P53核转位调控肠癌SW480细胞凋亡[J]. 第三军医大学学报, 2017,39(8):787-793.
Weiwen Yang, Yue Zhang, Xiong Xie, et al. Fibronectin extra domain A suppresses apoptosis of colorectal cancer SW480 cells by inhibiting P53 nuclear translocation[J]. Journal of Third Military Medical University, 2017, 39(8): 787-793.
杨卫文, 张月, 谢雄, 等. 纤维粘连蛋白EDA片段抑制P53核转位调控肠癌SW480细胞凋亡[J]. 第三军医大学学报, 2017,39(8):787-793. DOI： 10.16016/j.1000-5404.201610068.
Weiwen Yang, Yue Zhang, Xiong Xie, et al. Fibronectin extra domain A suppresses apoptosis of colorectal cancer SW480 cells by inhibiting P53 nuclear translocation[J]. Journal of Third Military Medical University, 2017, 39(8): 787-793. DOI： 10.16016/j.1000-5404.201610068.
摘要
Abstract
Objective
2
To investigate the role of fibronectin extra domain a (FN-EDA) in regulating the apoptosis of colorectal cancer cells and explore the possible mechanism.
Methods
2
Gene set enrichment analysis (GSEA) was used to analyze the microarray data of colorectal cancer with high and low FN-EDA expression. In a colorectal cancer cell line SW480 with lentiviral vector-mediated FN-EDA knockdown
the transcription levels of
P53
BAX
and
P 21
were assayed using real-time PCR
and the protein expression levels of P53
BAX
P21
Cleaved caspase-3
p-P53 (Ser15)
p-P53 (Ser37) and p-P53 (Ser392) were detected with Western blotting. Flow cytometry was used to detect the changes of cell apoptosis following FN-EDA knockdown
and the subcellular distribution of P53 was observed by immunofluorescence assay; the interaction between FN-EDA and P53 was analyzed using co-immunoprecipitation assay.
Results
2
The genesets of KEGG_APOPTOSIS were obviously enriched and up-regulated in colorectal canc
er cells with low FN-EDA expression (
P
<
0.05). Compared with the control cells
the cells with FN-EDA knockdown showed significantly increased protein levels of P53
BAX
P21
Cleaved caspase-3
p-P53 (Ser15)
p-P53 (Ser37) and p-P53 (Ser392) with also increased apoptotic rate (
P
<
0.05); FN-EDA knockdown also resulted in significantly increased nuclear translocation of P53 as shown by immunofluorescence assay and Western blotting. Over-expression of FN-EDA in the cells with FN-EDA knockdown significantly inhibited the cell apoptosis (
P
<
0.05)
induced down-regulation of P53
p-P53 (Ser15)
p-P53 (Ser37) and BAX
and decreased nuclear translocation of P53. Co-immunoprecipitation assay showed a direct interaction between P53 and FN-EDA.
Conclusion
2
FN-EDA inhibits nuclear traslocation and phosphrylation of P53
via
a direct interaction with P53 to regulate P53-BAX pathway and suppress the apoptosis of colorectal cancer SW480 cells.
关键词
Keywords
references
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