hTERT promotes gastric intestinal metaplasia by upregulating CDX2 via NF-κB signaling pathway.
hTERT promotes gastric intestinal metaplasia by upregulating CDX2 via NF-κB signaling pathway.
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hTERT 通过 NF-kappa B 信号通路上调 CDX2 促进胃肠化生
DOI：
10.18632/oncotarget.15926
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发表时间：
2017-04-18
期刊：
影响因子：
--
通讯作者：
Yang SM
中科院分区：
文献类型：
--
作者：
Chen BJ;Zeng S;Xie R;Hu CJ;Wang SM;Wu YY;Xiao YF;Yang SM
已有研究表明hTERT参与胃癌的增殖和转移，但hTERT在胃粘膜癌前病变--胃肠上皮化生中的作用尚不清楚。本研究的目的是探讨hTERT在GIM中的作用以及hTERT对胃细胞CDX 2表达的影响。实验结果表明，胃肠道间质瘤中hTERT的表达明显高于正常胃粘膜。此外，hTERT还通过NF-κB增加GIM过程中KLF 4的表达。此外，KLF 4参与了hTERT诱导的CDX 2的上调，hTERT可以与p50相互作用，从而增加CDX 2的水平。采用免疫组化法检测肠上皮化生组织中hTERT的表达。通过qRT-PCR、WB和双荧光素酶实验检测hTERT对CDX 2表达的影响。用WB、CO-IP和ChIP进一步检测p65和p50在CDX 2调控中的作用。结论：hTERT通过NF-κB信号通路上调CDX 2表达，促进GIM的发生。
hTERT has been reported involved in the proliferation and metastasis of gastric cancer, but the role of hTERT in gastric intestinal metaplasia, a premalignant lesion of the gastric mucosa was unknown. The aim of the present study was to investigate the role of hTERT in GIM and the effect of hTERT on CDX2 expression in gastric cells. Experiments showed that expression of hTERT was significantly higher in GIM than in normal gastric mucosa. Moreover, hTERT increased the KLF4 level via NF-κB during GIM. Furthermore, KLF4 is involved in the up-regulation of CDX2 induced by hTERT, and hTERT can interact with p50, thereby increasing the level of CDX2. Immunohistochemistry was used to detect the expression of hTERT in gastric intestinal metaplasia tissue. Then, effect of hTERT on the expression of CDX2 was detected by qRT-PCR, WB and dual luciferase experiment. The role of p65 and p50 in the regulation of CDX2 were further detected by WB, CO-IP and ChIP. We may conclude that hTERT promotes GIM by up-regulating CDX2 via NF-κB signaling pathway.