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DDIT4 promotes gastric cancer proliferation and tumorigenesis through the p53 and MAPK pathways.


ABSTRACT:

Background

Gastric cancer (GC) is one of the most common malignancies worldwide, particularly in China. DNA damage-inducible transcript 4 (DDIT4) is a mammalian target of rapamycin inhibitor and is induced by various cellular stresses; however, its critical role in GC remains poorly understood. The present study aimed to investigate the potential relationship and the underlying mechanism between DDIT4 and GC development.

Methods

We used western blotting, real-time polymerase chain reaction, and immunohistochemical or immunofluorescence to determine DDIT4 expression in GC cells and tissues. High-content screening, cell counting kit-8 assays, colony formation, and in vivo tumorigenesis assays were performed to evaluate cell proliferation. Flow cytometry was used to investigate cell apoptosis and cell cycle distribution.

Results

DDIT4 was upregulated in GC cells and tissue. Furthermore, downregulating DDIT4 in GC cells inhibited proliferation both in vitro and in vivo and increased 5-fluorouracil-induced apoptosis and cell cycle arrest. In contrast, ectopic expression of DDIT4 in normal gastric epithelial cells promoted proliferation and attenuated chemosensitivity. Further analysis indicated that the mitogen-activated protein kinase and p53 signaling pathways were involved in the suppression of proliferation, and increased chemosensitivity upon DDIT4 downregulation.

Conclusion

DDIT4 promotes GC proliferation and tumorigenesis, providing new insights into the role of DDIT4 in the tumorigenesis of human GC.

SUBMITTER: Du F 

PROVIDER: S-EPMC6034313 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Publications

DDIT4 promotes gastric cancer proliferation and tumorigenesis through the p53 and MAPK pathways.

Du Feng F   Sun Lina L   Chu Yi Y   Li Tingyu T   Lei Chao C   Wang Xin X   Jiang Mingzuo M   Min Yali Y   Lu Yuanyuan Y   Zhao Xiaodi X   Nie Yongzhan Y   Fan Daiming D  

Cancer communications (London, England) 20180705 1


<h4>Background</h4>Gastric cancer (GC) is one of the most common malignancies worldwide, particularly in China. DNA damage-inducible transcript 4 (DDIT4) is a mammalian target of rapamycin inhibitor and is induced by various cellular stresses; however, its critical role in GC remains poorly understood. The present study aimed to investigate the potential relationship and the underlying mechanism between DDIT4 and GC development.<h4>Methods</h4>We used western blotting, real-time polymerase chain  ...[more]

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