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Induction of anion exchanger-1 translation and its opposite roles in the carcinogenesis of gastric cancer cells and differentiation of K562 cells

Oncogene volume 29, pages 1987–1996 (2010)Cite this article

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Abstract

Anion exchanger-1 (AE1), an erythroid-specific membrane protein, mediates the Cl−/HCO−3 exchange across the plasma membrane and regulates intracellular pH. We have found that AE1 was unexpectedly expressed in gastric cancer cells and participated in the tumorigenesis of the cancer. Here, we focus on the induction of AE1 expression and its role in gastric carcinogenesis as well as in the differentiation of K562 cells. The results show that expression of AE1 is not related to genetic mutation or the mRNA level, but rather, that it is modulated by miR-24. miR-24 decreases the expression of AE1 through binding to the 3′UTR of AE1 mRNA. Transfection of an miR-24 into gastric cancer cells reduced the elevation of the AE1 protein, which resulted in return of AE1-sequestrated p16 to the nucleus, thereby inhibiting proliferation of the cells. Furthermore, the miR-24 inhibitor cooperated with hemin to induce the expression of AE1 in K562 cells and differentiation of the cells, which is consistent with results obtained from the cells cultured at pH 7.6 or from forced stable expression of AE1. These findings establish a novel regulation of miR-24-related AE1 expression in gastric carcinogenesis and erythropoiesis.

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Acknowledgements

This work was supported in part by the National Natural Science Foundation of China (NO30570697, NO30770960) and National High Technology Research and Development Program of China (863 Program) (NO2008AA02Z120).

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  1. J Wu, Y-C Zhang and W-H Suo: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Pathology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China

    J Wu, Y-C Zhang, W-H Suo, W-W Shen, H Tian & G-H Fu

  2. Department of Radiation, Oncology of the 2nd Affiliated Hospital, Harbin Medical University, Harbin, PR China

    X-B Liu

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  1. J Wu
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  2. Y-C Zhang
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  6. H Tian
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Correspondence to G-H Fu.

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Wu, J., Zhang, YC., Suo, WH. et al. Induction of anion exchanger-1 translation and its opposite roles in the carcinogenesis of gastric cancer cells and differentiation of K562 cells. Oncogene 29, 1987–1996 (2010). https://doi.org/10.1038/onc.2009.481

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