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首页> 外文期刊>Biology Open >Effects of β4 integrin expression on microRNA patterns in breast cancer
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Effects of β4 integrin expression on microRNA patterns in breast cancer

机译：β4整合素表达对乳腺癌微RNA模式的影响

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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.
机译：整联蛋白α6β4被定义为层粘连蛋白的粘附受体。这种整合素被称为“β4”，它通过协调关键信号转导事件并促进细胞运动而在各种癌症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子，对microRNA（miRNA）进行了研究，原因是它们与肿瘤发生有着广泛的联系，并且能够调节全球基因表达。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分析（qNPA）的新型miRNA微阵列分析显示，β4表达可显着改变miRNA表达，并鉴定了两个miRNA家族，即miR-25 / 32 / 92abc / 363 / 363-3p / 367和miR-99ab / 100，该整合素的表达始终下调了这些蛋白。对已发布的Affymetrix基因芯片数据的分析确定了β4调控的mRNA子集中的miR-92ab和miR-99ab / 100的54个共同靶标，揭示了一些已知的基因，这些基因是β4调控的信号级联反应和细胞运动效应器的关键组成部分。基因本体论分类确定了与该群体内的细胞迁移相关的基因的富集。最后，对所有受β4调节的mRNA的基因集富集分析表明，属于不同miRNA家族的靶标中有富集，包括miR-92ab和我们最初的阵列分析所鉴定的其他靶标。这项研究中获得的结果提供了一个整合素在全球范围内影响miRNA表达的第一个例子，并提供了证据表明选择的miRNA家族共同靶向在执行β4介导的细胞运动中重要的基因。

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