Induction of anion exchanger-1 translation and its opposite roles in the carcinogenesis of gastric cancer cells and differentiation of K562 cells
Induction of anion exchanger-1 translation and its opposite roles in the carcinogenesis of gastric cancer cells and differentiation of K562 cells
复制标题
阴离子交换剂1翻译诱导及其在胃癌细胞癌变和K562细胞分化中的相反作用
DOI：
10.1038/onc.2009.481
复制
发表时间：
2010-04-01
期刊：
影响因子：
8
通讯作者：
Fu, G-H
中科院分区：
文献类型：
--
作者：
Wu, J.;Zhang, Y-C;Fu, G-H
阴离子交换蛋白-1（AE 1）是一种红系特异性膜蛋白，介导Cl（-）/HCO（3）（-）跨膜交换，调节细胞内pH值。在这里，我们集中在AE 1的表达诱导及其在胃癌的发生，以及在K562细胞的分化中的作用。结果表明，AE 1的表达与基因突变或mRNA水平无关，而是受到miR-24的调节。miR-24通过与AE 1 mRNA的3 'UTR结合降低AE 1的表达。将miR-24转染到胃癌细胞中降低了AE 1蛋白的升高，这导致AE 1螯合的p16返回到细胞核，从而抑制了细胞的增殖。此外，miR-24抑制剂与氯化血红素协同诱导K562细胞中AE 1的表达和细胞的分化，这与从在pH 7.6下培养的细胞或从AE 1的强制稳定表达获得的结果一致。这些发现建立了胃癌发生和红细胞生成中miR-24相关AE 1表达的新调控。Oncogene（2010）29，1987-1996; doi：10.1038/onc.2009.481; 2010年1月11日在线发表
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. Oncogene (2010) 29, 1987-1996; doi:10.1038/onc.2009.481; published online 11 January 2010