MicroRNA and HER2-overexpressing cancer.
MicroRNA and HER2-overexpressing cancer.
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DOI：
10.2174/22115366113029990011
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发表时间：
2013
影响因子：
--
通讯作者：
Lin RJ
中科院分区：
文献类型：
--
作者：
Wang SE;Lin RJ
microRNA（miRNAs）的发现为在分子水平上研究癌症开辟了新的途径，标志着生物医学研究的后基因组时代。这些约22个核苷酸的非编码调节RNA分子已成为重要的癌症生物标志物、效应物和靶标。在这篇综述中，我们专注于原癌基因HER 2过表达的癌症中miRNAs的生物发生和功能失调。这里回顾的许多研究都是在乳腺癌中进行的，其中HER 2过表达已经被广泛研究，HER 2靶向治疗已经实施了十多年。已经报道了可用于对具有不同HER 2状态的肿瘤进行分类的miRNA特征，但在各种研究中几乎没有达成共识，强调需要在大型和平衡良好的患者队列中进行额外的良好控制的分析方法和荟萃分析。我们进一步讨论了microRNA失调在HER 2相关恶性肿瘤或治疗中的三个方面：（a）由HER 2上调或下调并介导HER 2下游信号传导的miRNA;（B）抑制HER 2或HER 2受体复合物中因子（如HER 3）表达的miRNA;（c）影响抗HER 2治疗反应的miRNA。主要使用miR-205、miR-125和miR-21的例子来阐述调控机制。理解miR在HER 2过表达肿瘤中的调节和功能将为microRNA和HER 2原癌基因在癌症中的致病机制以及个体化或组合抗HER 2治疗提供新的思路。
The discovery of microRNAs (miRNAs) has opened up new avenues for studying cancer at the molecular level, featuring a post-genomic era of biomedical research. These non-coding regulatory RNA molecules of ~22 nucleotides have emerged as important cancer biomarkers, effectors, and targets. In this review, we focus on the dysregulated biogenesis and function of miRNAs in cancers with an overexpression of the proto-oncogene HER2. Many of the studies reviewed here were carried out in breast cancer, where HER2 overexpression has been extensively studied and HER2-targeted therapy practiced for more than a decade. MiRNA signatures that can be used to classify tumors with different HER2 status have been reported but little consensus can be established among various studies, emphasizing the needs for additional well-controlled profiling approaches and meta-analyses in large and well-balanced patient cohorts. We further discuss three aspects of microRNA dysregulation in or contribution to HER2-associated malignancies or therapies: (a) miRNAs that are up- or down-regulated by HER2 and mediate the downstream signaling of HER2; (b) miRNAs that suppress the expression of HER2 or a factor in HER2 receptor complexes, such as HER3; and (c) miRNAs that affect responses to anti-HER2 therapies. The regulatory mechanisms are elaborated using mainly examples of miR-205, miR-125, and miR-21. Understanding the regulation and function of miRNAs in HER2-overexpressing tumors shall shed new light on the pathogenic mechanisms of microRNAs and the HER2 proto-oncogene in cancer, as well as on individualized or combinatorial anti-HER2 therapies.