Oncotarget

Research Papers:

hTERT promotes gastric intestinal metaplasia by upregulating CDX2 via NF-κB signaling pathway

Bai-Jun Chen, Shuo Zeng, Rui Xie, Chang-Jiang Hu, Su-Ming Wang, Yu-Yun Wu, Yu-Feng Xiao and Shi-Ming Yang _

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Oncotarget. 2017; 8:26969-26978. https://doi.org/10.18632/oncotarget.15926

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Abstract

Bai-Jun Chen1,2,*, Shuo Zeng1,*, Rui Xie1, Chang-Jiang Hu1, Su-Ming Wang1, Yu-Yun Wu1, Yu-Feng Xiao1, Shi-Ming Yang1

1Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, PR China

2Department of Gastroenterology, The First Affiliated Hospital, Chengdu Medical College, Chengdu, PR China

*These authors contributed equally to this work

Correspondence to:

Shi-Ming Yang, email: [email protected]

Yu-Feng Xiao, email: [email protected]

Keywords: hTERT, KLF4, CDX2, gastric intestinal metaplasia, NF-κB

Received: January 05, 2017     Accepted: February 20, 2017     Published: March 06, 2017

ABSTRACT

Background: 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.

Results: 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.

Materials and Methods: 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.

Conclusions: We may conclude that hTERT promotes GIM by up-regulating CDX2 via NF-κB signaling pathway.


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