MicroRNAs in Melanoma Biology
MicroRNAs in Melanoma Biology
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DOI：
10.1007/978-94-007-5590-1_6
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发表时间：
2013-01-01
期刊：
影响因子：
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通讯作者：
Kunz, Manfred
中科院分区：
文献类型：
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作者：
Kunz, Manfred
恶性黑色素瘤是一种高度侵袭性的肿瘤，在转移期发病率增加，预后差。近年来，大量关于单个miRNA或miRNA模式的报道已经发表，提供了强有力的证据，证明miRNA可能在恶性黑色素瘤中发挥重要作用，并可能有助于更好地了解黑色素瘤发生和进展的分子机制。一项主要的初步发现是，黑色素瘤相关的mirna通常位于肿瘤中频繁获得和丢失的基因组区域。随后，不同组的详细研究发现，与黑色素瘤细胞系相比，良性黑色素细胞或良性黑色素细胞病变与黑色素瘤相比，miRNAs在良性黑色素细胞中表达差异。其中有let-7a和b、miR-23a和b、miR-148、miR-155、miR-182、miR-200c、miR-211、miR214和miR-221和222。其中一些mirna靶向众所周知的黑色素瘤相关基因，如NRAS癌基因、小眼相关转录因子（MITF）、受体酪氨酸激酶c-KIT或AP-2转录因子（TFAP2）。尽管我们还远未完全了解mirna -靶基因相互作用在恶性黑色素瘤中的作用，但这些发现进一步强调了mirna直接参与黑色素瘤生物学的概念。最近，已经确定了六种mirna的预后特征，包括miR-150， miR-342-3p, miR-455-3p, miR-145， miR-155和miR-497。这些mirna的高表达被证明与转移性患者的长期生存改善有关。
Malignant melanoma is a highly aggressive tumour with increasing incidence and poor prognosis in the metastatic stage. In recent years, a substantial number of reports on individual miRNAs or miRNA patterns have been published providing strong evidence that miRNAs might play an important role in malignant melanoma and might help to better understand the molecular mechanisms of melanoma development and progression. A major preliminary finding was that melanoma-associated miRNAs are often located in genomic regions with frequent gains and losses in tumours. Detailed studies of different groups thereafter identified miRNAs with differential expression in benign melanocytes compared with melanoma cell lines or in benign melanocytic lesions compared with melanomas. Among these were let-7a and b, miR-23a and b, miR-148, miR-155, miR-182, miR-200c, miR-211, miR214, and miR-221 and 222. Some of these miRNAs target well-known melanoma-associated genes like the NRAS oncogene, microphthalmia-associated transcription factor (MITF), receptor tyrosine kinase c-KIT or AP-2 transcription factors (TFAP2). Although we are still far from a complete understanding of the role of miRNA-target gene interactions in malignant melanoma, these findings further underscore the notion of a direct involvement of miRNAs in melanoma biology. Very recently, a prognostic signature of six miRNAs has been identified consisting of miRNAs miR-150, miR-342-3p, miR-455-3p, miR-145, miR-155, and miR-497. High expression of these miRNAs was shown to be associated with improved long-term survival of metastatic patients.