HuR is exported to the cytoplasm in oral cancer cells in a different manner from that of normal cells.
HuR is exported to the cytoplasm in oral cancer cells in a different manner from that of normal cells.
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DOI：
10.1038/sj.bjc.6605084
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发表时间：
2009-06-16
影响因子：
8.8
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中科院分区：
文献类型：
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作者：
HuR是Hu蛋白家族的一个广泛表达的成员，其结合并稳定含有富含AU元件（ARE）的mRNAs，已知其通过几种输出途径在细胞核和细胞质之间穿梭。当正常细胞用热休克处理时，HuR以染色体维持区1（CRM 1）依赖的方式输出到细胞质。然而，在这项研究中，我们证明了HuR被输出到口腔癌细胞的细胞质中，即使细胞用CRM 1-独立输出途径的抑制剂处理。免疫组化和生化分析表明，HuR在口腔癌细胞（如HSC-3和Ca9.22）中既存在于胞浆中，也存在于胞核中，而在正常细胞中完全存在于胞核中。富含AU的元件-mRNA也被输出到细胞质并在口腔癌细胞中稳定，其被HuR敲低抑制。HuR的这种输出不受至少7小时的来普霉素B（LMB）处理的影响，来普霉素B是CRM 1依赖性输出途径的抑制剂。这些研究结果表明，HuR出口到细胞质中的口腔癌细胞以不同的方式从正常细胞，并可能发生通过正常的出口途径的扰动。
HuR, a ubiquitously expressed member of the Hu protein family that binds and stabilizes an AU-rich element (ARE)-containing mRNAs, is known to shuttle between the nucleus and the cytoplasm via several export pathways. When normal cells were treated with heat shock, HuR was exported to the cytoplasm in a chromosome maintenance region 1 (CRM1)-dependent manner. However, in this study, we demonstrate that HuR is exported to the cytoplasm in oral cancer cells even if the cells were treated with the inhibitor of the CRM1-independent export pathway. Immunohistochemical and biochemical analyses showed that HuR existed in both the cytoplasm and the nucleus in oral cancer cells, such as HSC-3 and Ca9.22, but existed entirely inside the nucleus in normal cells. AU-rich element-mRNAs were also exported to the cytoplasm and stabilised in the oral cancer cells, which were inhibited by HuR knockdown. This export of HuR was not affected by at least 7 h of treatment of leptomycin B (LMB), which is an inhibitor of the CRM1-dependent export pathway. These findings suggest that HuR is exported to the cytoplasm in oral carcinoma cells in a different manner from that of normal cells, and is likely to occur through the perturbation of a normal export pathway.