HuR keeps an angiogenic switch on by stabilising mRNA of VEGF and COX-2 in tumour endothelium.
HuR keeps an angiogenic switch on by stabilising mRNA of VEGF and COX-2 in tumour endothelium.
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DOI：
10.1038/bjc.2011.20
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发表时间：
2011-03-01
影响因子：
8.8
通讯作者：
Hida, K.
中科院分区：
文献类型：
--
作者：
Kurosu, T.;Ohga, N.;Hida, Y.;Maishi, N.;Akiyama, K.;Kakuguchi, W.;Kuroshima, T.;Kondo, M.;Akino, T.;Totsuka, Y.;Shindoh, M.;Higashino, F.;Hida, K.
肿瘤基质细胞不同于正常基质细胞。我们已经表明，从肿瘤组织中分离的肿瘤内皮细胞（TECs）也异常。此外，我们发现血管内皮生长因子- a （VEGF-A）和环氧化酶-2 (COX-2) mrna在tec中上调。血管内皮生长因子- a和COX-2是血管生成因子，它们的mrna含有富au元素（are）。据报道，富含au元素的mrna被Hu抗原R （HuR）稳定，并输出到细胞质。分离正常内皮细胞（NEC）和两种类型的内皮细胞（tec）。我们评估了HuR与tec中VEGF-A和COX-2 mrna积累的相关性，以及HuR对tec生物学表型的影响。HuR蛋白在tec细胞质中积累，而在nec细胞质中没有。血管内皮生长因子- a和COX-2 mRNA水平由于HuR敲低而降低，并且这些ARE-mRNA在tec中与HuR结合。此外，HuR敲低抑制TECs细胞存活、随机运动、管形成和Akt磷酸化。Hu抗原R与TECs中VEGF-A和COX-2 mRNA的上调有关，并通过激活肿瘤内皮中的血管生成表型，在保持血管生成开关打开方面发挥重要作用。
Tumour stromal cells differ from its normal counterpart. We have shown that tumour endothelial cells (TECs) isolated from tumour tissues are also abnormal. Furthermore, we found that mRNAs of vascular endothelial growth factor-A (VEGF-A) and cyclooxygenase-2 (COX-2) were upregulated in TECs. Vascular endothelial growth factor-A and COX-2 are angiogenic factors and their mRNAs contain an AU-rich element (ARE). AU-rich element-containing mRNAs are reportedly stabilised by Hu antigen R (HuR), which is exported to the cytoplasm. Normal endothelial cell (NEC) and two types of TECs were isolated. We evaluated the correlation of HuR and accumulation of VEGF-A and COX-2 mRNAs in TECs and effects of HuR on biological phenotypes of TECs. The HuR protein was accumulated in the cytoplasm of TECs, but not in NECs. Vascular endothelial growth factor-A and COX-2 mRNA levels decreased due to HuR knockdown and it was shown that these ARE-mRNA were bound to HuR in TECs. Furthermore, HuR knockdown inhibited cell survival, random motility, tube formation, and Akt phosphorylation in TECs. Hu antigen R is associated with the upregulation of VEGF-A and COX-2 mRNA in TECs, and has an important role in keeping an angiogenic switch on, through activating angiogenic phenotype in tumour endothelium.
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