Pawlina Klaudia, Gurgul Artur, Szmatoła Tomasz, Koch Christoph, Mählmann Kathrin, Witkowski Maciej, Bugno-Poniewierska Monika
Laboratory of Genomics, Department of Animal Genomics and Molecular Biology, National Research Institute of Animal Production, Krakowska 1, 32-083, Balice, Poland.
Swiss Institute of Equine Medicine ISME, Faculty of Veterinary Medicine, University of Bern and Agroscope, Länggassstrasse 124c, Postfach 8466, CH-3001, Bern, Switzerland.
Biochimie. 2017 Jun;137:20-28. doi: 10.1016/j.biochi.2017.02.017. Epub 2017 Mar 1.
Equine sarcoids are the most common neoplasms occurring in horses. Despite frequent occurrence, they are still not well described at the molecular level. Thus, in the present study, we performed a comprehensive comparative analysis of sarcoid miRNAome profile to identify aberrantly expressed microRNAs, along with their structural variants, potentially useful as biomarkers and, in a wider perspective, broaden the knowledge about this tumor and underlying mechanisms. To this end, we conducted next generation sequencing and as a result we identified both known and potentially novel miRNAs. Differential expression analysis revealed the existence of almost one hundred miRNAs being over- or underexpressed in sarcoids in comparison to healthy tissue (p-adj<0.05), of which many are known for their involvement in processes crucial for neoplastic transformation. Among upregulated miRNAs there were those associated with decreased cell adhesion abilities as well as engaged in global protein production, while downregulation of some miRs i.a. increased cell expansion abilities. Moreover, we identified altered expression levels of miRNA variants (isomiRs) between the investigated tissues. Further analysis revealed that 5' isomiRs comprise different seed sequences leading to target gene switching followed by activation of different biological pathways. Our results are the first which revealed the complexity of microRNA profiles in equine sarcoids and skin tissue, along with the dynamism of their growing in importance concomitants, namely isomiRs. They also showed miRNA molecules and biological pathways important from the sarcoid oncogenesis point of view.
马肉瘤是马最常见的肿瘤。尽管其发病率很高，但在分子水平上仍未得到充分描述。因此，在本研究中，我们对肉瘤的miRNA组谱进行了全面的比较分析，以鉴定异常表达的 microRNA 及其结构变体，这些变体可能作为生物标志物，并且从更广泛的角度拓宽对这种肿瘤及其潜在机制的认识。为此，我们进行了下一代测序，结果鉴定出了已知的和潜在的新型miRNA。差异表达分析显示，与健康组织相比，肉瘤中存在近100种miRNA表达上调或下调（p值校正<0.05），其中许多已知参与肿瘤转化的关键过程。上调的miRNA中，有些与细胞黏附能力降低以及整体蛋白质产生有关，而一些miRNA的下调则增加了细胞扩张能力。此外，我们还鉴定出了被研究组织之间miRNA变体（isomiRs）的表达水平变化。进一步分析表明，5' isomiRs包含不同的种子序列，导致靶基因切换，进而激活不同的生物学途径。我们的结果首次揭示了马肉瘤和皮肤组织中 microRNA 谱的复杂性，以及其重要性日益增加的伴随物（即isomiRs）的动态变化。这些结果还显示了从肉瘤肿瘤发生角度来看重要的miRNA分子和生物学途径。
