Effects of β4 integrin expression on microRNA patterns in breast cancer.
Effects of β4 integrin expression on microRNA patterns in breast cancer.
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DOI：
10.1242/bio.20121628
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发表时间：
2012-07-15
期刊：
影响因子：
2.4
通讯作者：
Mercurio AM
中科院分区：
文献类型：
--
作者：
Gerson KD;Maddula VS;Seligmann BE;Shearstone JR;Khan A;Mercurio AM
整合素α6β4被定义为层粘连蛋白的粘附受体。被称为“β 4”，这种整合素通过其协调关键信号转导事件和促进细胞运动的能力在各种癌的进展中起关键作用。为了鉴定乳腺癌中β4功能的新型下游效应物，研究了microRNA（miRNAs），因为它们与肿瘤发生的广泛联系以及它们在全局上调节基因表达的能力。使用两种乳腺癌细胞系和一组具有不同β4表达的浸润性乳腺癌来评估这种整合素对miRNA表达的影响。一种称为定量核酸酶保护试验（qNPA）的新的miRNA微阵列分析揭示了β4表达可以显著改变miRNA表达，并鉴定了两个miRNA家族，miR-25/32/92 abc/363/363- 3 p/367和miR-99 ab/100，其通过该整合素的表达而持续下调。通过分析已发表的Affyssin基因芯片数据，在β4调节的mRNA亚组中鉴定了miR-92 ab和miR-99 ab/100的54个共同靶点，揭示了已知是β4调节的信号级联和细胞运动效应器的关键组分的几个基因。基因本体分类鉴定了该群体中与细胞迁移相关的基因的富集。最后，所有β4调节的mRNA的基因集富集分析揭示了属于不同miRNA家族的靶点的富集，包括miR-92 ab和我们最初的阵列分析鉴定的其他靶点。本研究中获得的结果提供了整合素全面影响miRNA表达的第一个例子，并提供了选择miRNA家族共同靶向执行β4介导的细胞运动重要基因的证据。
The integrin α6β4 is defined as an adhesion receptor for laminins. Referred to as ‘β4’, this integrin plays a key role in the progression of various carcinomas through its ability to orchestrate key signal transduction events and promote cell motility. To identify novel downstream effectors of β4 function in breast cancer, microRNAs (miRNAs) were examined because of their extensive links to tumorigenesis and their ability to regulate gene expression globally. Two breast carcinoma cell lines and a collection of invasive breast carcinomas with varying β4 expression were used to assess the effect of this integrin on miRNA expression. A novel miRNA microarray analysis termed quantitative Nuclease Protection Assay (qNPA) revealed that β4 expression can significantly alter miRNA expression and identified two miRNA families, miR-25/32/92abc/363/363-3p/367 and miR-99ab/100, that are consistently downregulated by expression of this integrin. Analysis of published Affymetrix GeneChip data identified 54 common targets of miR-92ab and miR-99ab/100 within the subset of β4-regulated mRNAs, revealing several genes known to be key components of β4-regulated signaling cascades and effectors of cell motility. Gene ontology classification identified an enrichment in genes associated with cell migration within this population. Finally, gene set enrichment analysis of all β4-regulated mRNAs revealed an enrichment in targets belonging to distinct miRNA families, including miR-92ab and others identified by our initial array analyses. The results obtained in this study provide the first example of an integrin globally impacting miRNA expression and provide evidence that select miRNA families collectively target genes important in executing β4-mediated cell motility.
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影响因子：
64.8
作者：
Lu, J;Getz, G;Golub, TR
通讯作者：
Golub, TR
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
DOI：
10.1093/bioinformatics/btn615
发表时间：
2009-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Carbon S;Ireland A;Mungall CJ;Shu S;Marshall B;Lewis S;AmiGO Hub;Web Presence Working Group
通讯作者：
Web Presence Working Group
影响因子：
7.3
作者：
Avraham, Roi;Sas-Chen, Aldema;Yarden, Yosef
通讯作者：
Yarden, Yosef
影响因子：
13.8
作者：
Hynes, RO
通讯作者：
Hynes, RO