The Cochrane Database of Systematic Reviews, Issue 4, 2010

doi:10.1111/j.1756-5391.2010.01079.x

Cited by 5 publications

(1 citation statement)

References 21 publications

(12 reference statements)

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“…Colorectal cancer (CRC) is one of the most common and fatal neoplastic diseases worldwide [1]. Although improved treatment strategies have increased the overall survival rates in the early stages, 5-year survival rates have not raised substantially in the past decades [2].…”

Section: Introductionmentioning

confidence: 99%

The SLC34A2-ROS-HIF-1-induced up-regulation of EZH2 expression promotes proliferation and chemo-resistance to apoptosis in colorectal cancer

Xing

Wang

et al. 2019

Bioscience Reports

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Growing evidence has uncovered that plays an evident role in the progression in several types of tumors. However, the biological function and underlying molecular mechanisms of remain largely unknown. Here, we indicated that SLC34A2 expression was markedly increased in SW480 and HT29 cell line cells compared with that in normal colorectal epithelial cell line cells. Array analysis displayed that the expression of EZH2 (enhancer of zeste 2) decreased considerably when was knocked-down. We demonstrated that SLC34A2 induced EZH2 expression and activated its promoter activity. Serial 5' deletion and site-directed mutagenesis revealed that the induction of EZH2 expression by SLC34A2 was dependent upon the hypoxia-inducible factor 1 (HIF1)-2 binding site directly within EZH2 promoter. Moreover, HIF-1 activation was proved essential for SLC34A2-induced EZH2 expression. Reactive oxygen species (ROS) generation contributed to the stabilization of HIF-1α by leading to the binding of HIF-1α to the EZH2 promoter, which resulted in increased EZH2 expression. Additionally, we showed that the inhibition of both HIF-1α expression and ROS generation by YC-1 or BHA, respectively, decreased SLC34A2-induced EZH2 overexpression. Significantly, SLC34A2-induced EZH2 overexpression promoted the proliferation and chemo-resistance to apoptosis in colorectal cancer cells in vitro and in vivo. Altogether, we conclude that the SLC34A2-ROS-HIF-1-induced overexpression of EZH2 promotes colorectal cancer cells proliferation and chemo-resistance to apoptosis. SLC34A2-ROS-HIF-1-EZH2 signaling pathway might serve as a novel therapeutic target against colorectal cancer.

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Section: Introductionmentioning

confidence: 99%