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基因的高表达可能通过下调肠型胃癌中的 Ras/ERK 信号通路促进细胞凋亡。

High expression of the gene might promote apoptosis through downregulation of the Ras/ERK signalling pathway in the intestinal type of gastric cancer.

机构信息

Guizhou University School of Medicine, Guiyang, Guizhou Province, China.

Department of Pathology, Guizhou Provincial People's Hospital, Guiyang, Guizhou Province, China.

出版信息

J Int Med Res. 2020 Mar;48(3):300060520909025. doi: 10.1177/0300060520909025.

DOI:10.1177/0300060520909025
PMID:32223671
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7133087/
Abstract

OBJECTIVE

To investigate the effect of the casein kinase 2 interacting protein 1 (CKIP-1) on the apoptosis of the intestinal type of gastric cancer (GC).

METHODS

The levels of CKIP-1 protein and the rates of apoptosis were measured in tissue samples of the intestinal type of GC and human GC cell lines. The rate of apoptosis and the protein levels of B cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), cleaved cysteinyl aspartate specific protease 3 (cleaved caspase-3), cleaved caspase-9, rat sarcoma (Ras), extracellular signal-regulated kinase 1 and 2 (ERK1/2) and phosphorylated extracellular signal-regulated kinase 1 and 2 (p-ERK1/2) were analysed in SGC7901 cells expressing CKIP-1 short hairpin RNA (shRNA; knockdown) and SGC7901 cells overexpressing CKIP-1.

RESULTS

The levels of CKIP-1 protein were significantly lower in the intestinal type of GC tissues compared with the samples of intestinal metaplasia. Both the levels of CKIP-1 protein and the levels of apoptosis decreased gradually with decreasing cell differentiation in the intestinal type of GC tissue and cell lines; and they were positively correlated. In the CKIP-1 shRNA group, the rate of apoptosis and the levels of Bax, cleaved caspase-3 and cleaved caspase-9 were decreased; and the levels of Bcl-2, Ras and the ratio of p-ERK/ERK were increased, compared with the control group. Opposite results were observed in the CKIP-1 overexpression group.

CONCLUSION

High levels of CKIP-1 protein may promote apoptosis in the intestinal type of GC, possibly via the downregulation of the Ras/ERK signalling pathway.

摘要

目的

研究酪蛋白激酶 2 相互作用蛋白 1(CKIP-1)对肠型胃癌(GC)细胞凋亡的影响。

方法

检测肠型 GC 组织和人 GC 细胞系中 CKIP-1 蛋白水平和细胞凋亡率,分析 CKIP-1 短发夹 RNA(shRNA;敲低)表达的 SGC7901 细胞和 CKIP-1 过表达的 SGC7901 细胞中 B 细胞淋巴瘤-2(Bcl-2)、Bcl-2 相关 X 蛋白(Bax)、半胱天冬氨酸特异性蛋白酶 3 剪切体(cleaved caspase-3)、剪切体 caspase-9、大鼠肉瘤(Ras)、细胞外信号调节激酶 1 和 2(ERK1/2)和磷酸化细胞外信号调节激酶 1 和 2(p-ERK1/2)的蛋白水平和细胞凋亡率。

结果

肠型 GC 组织中 CKIP-1 蛋白水平明显低于肠化生组织。肠型 GC 组织和细胞系中 CKIP-1 蛋白水平和细胞凋亡率随细胞分化程度逐渐降低而逐渐降低,且呈正相关。在 CKIP-1 shRNA 组中,与对照组相比,细胞凋亡率、Bax、cleaved caspase-3 和 cleaved caspase-9 的蛋白水平降低,Bcl-2、Ras 和 p-ERK/ERK 比值增加。在 CKIP-1 过表达组中观察到相反的结果。

结论

CKIP-1 蛋白水平升高可能通过下调 Ras/ERK 信号通路促进肠型 GC 的细胞凋亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a955/7133087/3848e53b2c01/10.1177_0300060520909025-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a955/7133087/26174d0a7590/10.1177_0300060520909025-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a955/7133087/81ccfb05917a/10.1177_0300060520909025-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a955/7133087/0a1826a40b17/10.1177_0300060520909025-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a955/7133087/5de3ca94ebac/10.1177_0300060520909025-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a955/7133087/1e5f9af1a36f/10.1177_0300060520909025-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a955/7133087/3848e53b2c01/10.1177_0300060520909025-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a955/7133087/26174d0a7590/10.1177_0300060520909025-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a955/7133087/81ccfb05917a/10.1177_0300060520909025-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a955/7133087/0a1826a40b17/10.1177_0300060520909025-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a955/7133087/5de3ca94ebac/10.1177_0300060520909025-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a955/7133087/1e5f9af1a36f/10.1177_0300060520909025-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a955/7133087/3848e53b2c01/10.1177_0300060520909025-fig6.jpg

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