The VHL-dependent regulation of microRNAs in renal cancer.
The VHL-dependent regulation of microRNAs in renal cancer.
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DOI：
10.1186/1741-7015-8-64
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发表时间：
2010-10-21
期刊：
影响因子：
9.3
通讯作者：
Gleadle JM
中科院分区：
文献类型：
--
作者：
Neal CS;Michael MZ;Rawlings LH;Van der Hoek MB;Gleadle JM
最常见的肾癌组织学类型，即肾透明细胞癌（cc RCC），与von Hippel-Lindau（VHL）肿瘤抑制因子的遗传和表观遗传变化相关。VHL失活导致低氧诱导因子（HIF）的诱导和基因表达的低氧模式。当与正常组织相比时，在几种肿瘤中观察到特异性microRNA（miRNA）的差异水平。鉴于VHL在肾癌形成中的核心作用，我们研究了肾癌中VHL依赖性的miRNA调控。通过微阵列分析具有突变VHL（RCC 4-VHL）和重新引入野生型VHL（RCC 4 + VHL）的肾细胞系RCC 4来确定cc RCC中VHL依赖性miRNA表达。除了受HIF-VHL系统调节的miR-210之外，还进一步研究了在RCC 4 + VHL中高度上调的5种miRNA和在RCC 4 + VHL中高度下调的5种miRNA。与邻近的正常组织相比，还在31 cc RCC肿瘤中测量了miRNA表达。在肿瘤组织中观察到miR-210、miR-155和miR-21表达的显著增加。miR-210水平还显示与HIF调节的mRNA、碳酸酐酶IX（CAIX）以及VHL突变或启动子甲基化相关。在miR-210表达和患者存活率之间观察到负相关，并且miR-210的推定靶点铁硫簇组装蛋白（ISCU 1/2）显示肿瘤中mRNA表达的倒数水平。我们已经鉴定了VHL调节的miRNA，并发现对于一些调节是HIF依赖性的，而对于另一些调节是HIF不依赖性的。当与正常组织相比时，在肾癌组织中也观察到这些miRNA（miR-210、miR-155、let-7i和miR-17-92簇的成员）中的几种的这种调控模式。miR-210在肾癌中的表达显著增加，并且其水平与患者生存率相关。miR-210水平和ISCU 1/2之间的负相关性为ISCU 1/2是miR-210的靶点的假设提供了支持，并且它可能有助于在肾（和其他）肿瘤中观察到的无氧呼吸。参见评论：http://www.biomedcentral.com/1741-7015/8/65
The commonest histological type of renal cancer, clear cell renal cell carcinoma (cc RCC), is associated with genetic and epigenetic changes in the von Hippel-Lindau (VHL) tumour suppressor. VHL inactivation leads to induction of hypoxia-inducible factors (HIFs) and a hypoxic pattern of gene expression. Differential levels of specific microRNAs (miRNAs) are observed in several tumours when compared to normal tissue. Given the central role of VHL in renal cancer formation, we examined the VHL-dependent regulation of miRNAs in renal cancer. VHL-dependent miRNA expression in cc RCC was determined by microarray analysis of renal cell line RCC4 with mutated VHL (RCC4-VHL) and reintroduced wild-type VHL (RCC4 + VHL). Five miRNAs highly upregulated in RCC4 + VHL and five miRNAs highly downregulated in RCC4 + VHL were studied further, in addition to miR-210, which is regulated by the HIF-VHL system. miRNA expression was also measured in 31 cc RCC tumours compared to adjacent normal tissue. A significant increase in miR-210, miR-155 and miR-21 expression was observed in the tumour tissue. miR-210 levels also showed a correlation with a HIF-regulated mRNA, carbonic anhydrase IX (CAIX), and with VHL mutation or promoter methylation. An inverse correlation was observed between miR-210 expression and patient survival, and a putative target of miR-210, iron-sulfur cluster assembly protein (ISCU1/2), shows reciprocal levels of mRNA expression in the tumours. We have identified VHL-regulated miRNAs and found that for some the regulation is HIF-dependent and for others it is HIF-independent. This pattern of regulation was also seen in renal cancer tissue for several of these miRNAs (miR-210, miR-155, let-7i and members of the miR-17-92 cluster) when compared with normal tissue. miR-210 showed marked increases in expression in renal cancer and levels correlated with patient survival. The inverse correlation between miR-210 levels and ISCU1/2 provides support for the hypothesis that ISCU1/2 is a target of miR-210 and that it may contribute to the anaerobic respiration seen in renal (and other) tumours. See Commentary: http://www.biomedcentral.com/1741-7015/8/65
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高迁移率A2是头颈鳞状细胞癌中miRNA-98的靶标。
影响因子：
37.3
作者：
Hebert, Carla;Norris, Kathleen;Scheper, Mark A;Nikitakis, Nikolaos;Sauk, John J
通讯作者：
Sauk, John J
DOI：
10.1073/pnas.93.18.9821
发表时间：
1996-09-03
影响因子：
11.1
作者：
Herman, JG;Graff, JR;Baylin, SB
通讯作者：
Baylin, SB
影响因子：
3.7
作者：
Favaro E;Ramachandran A;McCormick R;Gee H;Blancher C;Crosby M;Devlin C;Blick C;Buffa F;Li JL;Vojnovic B;Pires das Neves R;Glazer P;Iborra F;Ivan M;Ragoussis J;Harris AL
通讯作者：
Harris AL
影响因子：
6.2
作者：
Gee, Harriet E.;Camps, Carme;Harris, Adrian L.
通讯作者：
Harris, Adrian L.
影响因子：
5
作者：
Hong, Seung-Beom;Furihata, Mutsuo;Schmidt, Laura S.
通讯作者：
Schmidt, Laura S.