Germ cell and tumor associated piRNAs in the medaka and Xiphophorus melanoma models.
Germ cell and tumor associated piRNAs in the medaka and Xiphophorus melanoma models.
复制标题
DOI：
10.1186/s12864-016-2697-z
复制
发表时间：
2016-05-17
期刊：
影响因子：
4.4
通讯作者：
Schartl M
中科院分区：
文献类型：
--
作者：
Kneitz S;Mishra RR;Chalopin D;Postlethwait J;Warren WC;Walter RB;Schartl M
越来越多的研究报告了Piwi相互作用RNA（piRNA）和皮尔纳加工酶Piwi在许多癌症中的异常表达。这一发现是快速分裂的肿瘤转化细胞的混乱分子生物学的附带现象，还是与肿瘤发生功能相关，目前还难以辨别。为了更好地理解piRNA在癌症发展中的作用，小型实验室鱼类模型可以做出有价值的贡献。然而，对鱼的体细胞和肿瘤组织中的piRNA知之甚少。为了鉴定可能参与黑色素瘤发病机制的皮尔纳簇，我们使用了几种青鳉和比目鱼/剑尾鱼杂交种的转基因品系，其发展了各种类型的黑色素瘤。在这些肿瘤中，Piwi根据肿瘤类型以不同水平表达。为了定量皮尔纳水平，对不同组织型的睾丸和黑素瘤的整个皮尔纳群体进行测序。由于青鳉或剑尾鱼的参考皮尔纳簇集还不可用，我们开发了一种软件管道来检测我们样品中的皮尔纳簇，并选择在一个或多个样品中富集的簇。我们发现几个基因座过度表达或下调不同的黑色素瘤亚型相比，色素沉着的皮肤。此外，聚类分析揭示了一个明确的区别睾丸，低级别和高级别的恶性黑色素瘤青。我们的数据暗示皮尔纳表达的失调可能与黑色素瘤的发展相关。我们的研究结果也加强了鱼类作为研究piRNA在肿瘤发生中作用的合适模型系统的重要性。本文的在线版本（doi：10.1186/s12864-016-2697-z）包含补充材料，可供授权用户使用。
A growing number of studies report an abnormal expression of Piwi-interacting RNAs (piRNAs) and the piRNA processing enzyme Piwi in many cancers. Whether this finding is an epiphenomenon of the chaotic molecular biology of the fast dividing, neoplastically transformed cells or is functionally relevant to tumorigenesisis is difficult to discern at present. To better understand the role of piRNAs in cancer development small laboratory fish models can make a valuable contribution. However, little is known about piRNAs in somatic and neoplastic tissues of fish. To identify piRNA clusters that might be involved in melanoma pathogenesis, we use several transgenic lines of medaka, and platyfish/swordtail hybrids, which develop various types of melanoma. In these tumors Piwi, is expressed at different levels, depending on tumor type. To quantify piRNA levels, whole piRNA populations of testes and melanomas of different histotypes were sequenced. Because no reference piRNA cluster set for medaka or Xiphophorus was yet available we developed a software pipeline to detect piRNA clusters in our samples and clusters were selected that were enriched in one or more samples. We found several loci to be overexpressed or down-regulated in different melanoma subtypes as compared to hyperpigmented skin. Furthermore, cluster analysis revealed a clear distinction between testes, low-grade and high-grade malignant melanoma in medaka. Our data imply that dysregulation of piRNA expression may be associated with development of melanoma. Our results also reinforce the importance of fish as a suitable model system to study the role of piRNAs in tumorigenesis. The online version of this article (doi:10.1186/s12864-016-2697-z) contains supplementary material, which is available to authorized users.