miRNA Expression Profiling in Melanocytes and Melanoma Cell Lines Reveals miRNAs Associated with Formation and Progression of Malignant Melanoma
miRNA Expression Profiling in Melanocytes and Melanoma Cell Lines Reveals miRNAs Associated with Formation and Progression of Malignant Melanoma
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DOI：
10.1038/jid.2008.452
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发表时间：
2009-07-01
影响因子：
6.5
通讯作者：
Bosserhoff, Anja K.
中科院分区：
文献类型：
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作者：
Mueller, Daniel W.;Rehli, Michael;Bosserhoff, Anja K.
尽管microRNA（miRNAs）的表达失调明显有助于所有类型的人类癌症的发展和进展，但关于恶性黑色素瘤中miRNAs表达水平变化的数据很少。在我们的研究中，我们对来自原发性肿瘤或转移性黑色素瘤的黑色素细胞和黑色素瘤细胞系进行了基于微阵列的miRNA分析。此外，我们分析了黑色素瘤细胞克隆的miRNA表达模式，其中黑色素瘤特异性基因的表达被反义技术稳定敲低。我们还生成了两个衍生物的黑色素瘤细胞系的miRNA表达谱，这两个衍生物的侵袭潜力不同。比较黑素细胞和黑色素瘤细胞系亚群的miRNA表达模式，我们鉴定了与恶性转化以及疾病进展和转移定植相关的大量miRNA。令人惊讶的是，大部分去调节最强烈的miRNA在肿瘤发展中并不重要。因此，我们的研究结果不仅提供了对黑色素细胞和黑色素瘤细胞系在黑色素瘤进展过程中miRnomes改变的见解，而且还提供了大量的miRNAs，以分析其作为诊断标志物或未来治疗靶点的潜力。
Although deregulated expression of microRNAs (miRNAs) demonstrably contributes to the development and progression of all types of human cancers, little data are available about the changes in miRNA expression levels in malignant melanoma. In our study, we performed microarray-based miRNA profiling of melanocytes and melanoma cell lines derived from either primary tumors or metastatic melanomas. In addition, we analyzed miRNA expression patterns of melanoma cell clones in which the expression of melanoma specific genes was stably knocked down by antisense techniques. We also generated miRNA expression profiles for two derivatives of a melanoma cell line that differ in their invasive potential. Comparing miRNA expression patterns of melanocytes and subsets of melanoma cell lines, we identified large cohorts of miRNAs associated with malignant transformation as well as with the progression of the disease and with metastatic colonization. Surprisingly, the bulk of miRNAs that deregulated most strongly was not described to be of importance in tumor development before. The results of our study, therefore, not only provide insights into alterations in the miRnomes of melanocytes and melanoma cell lines during melanoma progression but also present a large assortment of miRNAs to be analyzed for their potential as diagnostic markers or targets for therapies in the future.