The RNA binding protein HuR differentially regulates unique subsets of mRNAs in estrogen receptor negative and estrogen receptor positive breast cancer.
The RNA binding protein HuR differentially regulates unique subsets of mRNAs in estrogen receptor negative and estrogen receptor positive breast cancer.
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DOI：
10.1186/1471-2407-10-126
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发表时间：
2010-04-06
期刊：
影响因子：
3.8
通讯作者：
Atasoy U
中科院分区：
文献类型：
--
作者：
Calaluce R;Gubin MM;Davis JW;Magee JD;Chen J;Kuwano Y;Gorospe M;Atasoy U
mRNA和蛋白质的稳态水平之间的不一致性已被归因于影响mRNA稳定性和翻译的转录后控制机制。传统的全基因组微阵列分析方法，分析稳态水平的mRNA，可能会错过重要的mRNA靶点，由于显着的转录后基因调控的RNA结合蛋白（RBP）。核糖组学方法，利用RNA免疫沉淀杂交到微阵列（RIP芯片），提供了全球性的识别不同的RBP的假定内源性mRNA的目标。HuR是一种RBP，其与不稳定mRNA（如原癌基因）的富含AU的元件（ARE）结合，促进其翻译成蛋白质。HuR已被证明在癌症进展中起作用，细胞质HuR水平升高与许多癌症（包括乳腺癌）的侵袭性增加和预后不良直接相关。HuR已被描述为控制癌症的几种获得性能力的基因，并被假设为肿瘤维持基因，允许癌症一旦建立就增殖。我们使用HuR RIP-Chip作为一种全面和系统的方法，在MCF-7（雌激素受体阳性，ER+）和MDA-MB-231（雌激素受体阴性，ER-）乳腺癌细胞系中检测乳腺癌靶基因。我们鉴定了单独或在两种细胞类型中发现的HuR相关mRNA的独特子集。通过定量RT-PCR和生物素下拉分析鉴定并验证了两种新的HuR靶点，CD 9和CALM 2 mRNA。这是第一份在野生型ER+和ER-乳腺癌中对HuR相关靶点进行全基因组并排比较的报告。我们在ER+和ER-乳腺癌细胞系中发现了不同的、差异表达的癌症相关基因子集，并注意到HuR对两种癌症相关基因的差异调节取决于细胞环境。
The discordance between steady-state levels of mRNAs and protein has been attributed to posttranscriptional control mechanisms affecting mRNA stability and translation. Traditional methods of genome wide microarray analysis, profiling steady-state levels of mRNA, may miss important mRNA targets owing to significant posttranscriptional gene regulation by RNA binding proteins (RBPs). The ribonomic approach, utilizing RNA immunoprecipitation hybridized to microarray (RIP-Chip), provides global identification of putative endogenous mRNA targets of different RBPs. HuR is an RBP that binds to the AU-rich elements (ARE) of labile mRNAs, such as proto-oncogenes, facilitating their translation into protein. HuR has been shown to play a role in cancer progression and elevated levels of cytoplasmic HuR directly correlate with increased invasiveness and poor prognosis for many cancers, including those of the breast. HuR has been described to control genes in several of the acquired capabilities of cancer and has been hypothesized to be a tumor-maintenance gene, allowing for cancers to proliferate once they are established. We used HuR RIP-Chip as a comprehensive and systematic method to survey breast cancer target genes in both MCF-7 (estrogen receptor positive, ER+) and MDA-MB-231 (estrogen receptor negative, ER-) breast cancer cell lines. We identified unique subsets of HuR-associated mRNAs found individually or in both cell types. Two novel HuR targets, CD9 and CALM2 mRNAs, were identified and validated by quantitative RT-PCR and biotin pull-down analysis. This is the first report of a side-by-side genome-wide comparison of HuR-associated targets in wild type ER+ and ER- breast cancer. We found distinct, differentially expressed subsets of cancer related genes in ER+ and ER- breast cancer cell lines, and noted that the differential regulation of two cancer-related genes by HuR was contingent upon the cellular environment.
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影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
5.3
作者：
Galban, Stefanie;Kuwano, Yuki;Gorospe, Myriam
通讯作者：
Gorospe, Myriam
影响因子：
11.5
作者：
Denkert, C;Weichert, W;Hauptmann, S
通讯作者：
Hauptmann, S
影响因子：
14.2
作者：
Casolaro, Vincenzo;Fang, Xi;Stellato, Cristiana
通讯作者：
Stellato, Cristiana
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y