hnRNP G elicits tumor-suppressive activity in part by upregulating the expression of Txnip
hnRNP G elicits tumor-suppressive activity in part by upregulating the expression of Txnip
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DOI：
10.1016/j.bbrc.2008.05.175
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发表时间：
2008-08-08
影响因子：
3.1
通讯作者：
Park, No-Hee
中科院分区：
文献类型：
--
作者：
Shin, Ki-Hyuk;Kim, Reuben H.;Park, No-Hee
异质核核糖核蛋白（hnRNP）是一种核酸结合蛋白，在DNA修复、端粒调控和转录基因调控中发挥重要作用。在此之前，我们发现hnRNP G在人口腔鳞状细胞癌细胞中具有肿瘤抑制活性。因此，hnRNPG靶基因的鉴定对于了解hnRNPG的功能及其抑瘤活性具有重要意义。在本研究中，我们确定了一个已知的肿瘤抑制基因，硫氧还蛋白相互作用蛋白（Txnip）基因作为hnRNP G的新靶点。在人鳞状细胞癌中，Txnip的表达被野生型hnRNP G上调，但不被抑制缺陷突变型hnRNP G（K22 R）上调。野生型hnRNP G在体内结合并反式激活Txnip启动子，而K22 R突变体则不结合并反式激活Txnip启动子。此外，在癌细胞中单独过表达Txnip导致在免疫受损小鼠中抑制锚定非依赖性生长和体内致瘤性，表明转化表型的逆转。这些研究表明hnRNP G促进Txnip的表达并介导其肿瘤抑制作用。(c)2008年爱思唯尔公司All rights reserved.
Heterogeneous nuclear ribonuclearproteins (hnRNPs) are nucleic acid-binding proteins and have critical roles in DNA repair, telomere regulation, and transcriptional gene regulation. Previously, we showed that hnRNP G has tumor-suppressive activity in human oral squamous cell carcinoma cells. Therefore, the identification of hnRNP G target genes is important for understanding the function of hnRNP G and its tumor-suppressive activity. In this study, we identify a known tumor suppressor gene, thioredoxin-interacting protein (Txnip) gene as a novel target of hnRNP G. Expression of Txnip is upregulated by wild-type (wt) hnRNP G but not by a suppression-defective mutant hnRNP G (K22R) in human squamous cell carcinoma. Wt hnRNP G binds and transactivates the Txnip promoter in vivo, whereas the K22R mutant does not. Furthermore, overexpression of Txnip alone in cancer cells leads to the inhibition of anchorage-independent growth and in vivo tumorigenicity in immunocompromised mice, suggesting a reversion of the transformation phenotype. These studies indicate that hnRNP G promotes the expression of Txnip and mediates its tumor-suppressive effect. (c) 2008 Elsevier Inc. All rights reserved.