Department of Molecular Pathology and Neuropathology, Medical University of Lodz, Lodz, Poland.
Department of Neurosurgery, Polish Mother Memorial Hospital Research Institute in Lodz, Lodz, Poland.
Folia Neuropathol. 2020;58(2):123-132. doi: 10.5114/fn.2020.96734.
Nowadays molecular investigations have a significant impact on the understanding of primary brain tumour biology,as well as on their classification and progress in the treatment modalities. Among novel type of biomarkers with potential therapeutic value, microRNAs (miRNAs) are considered in some cases. miRNAs are small molecules regu-lating gene expression, including genes encoding key proteins involved in signalling pathways responsible for growth and cell survival during tumour formation. Incorrectly hyperactivated pathways implicated in brain tumour development are inter alia the PI3K/AKT/mTOR and RAS/MAPK/ERK cascades associated with worse prognosis and decreased patient survival. This work presents relationships between changes in the expression of individual miRNAs and the genes involved in the regulation of PI3K/AKT/mTOR and RAS/MAPK/ERK signalling pathways in primary brain tumours. Herein we present the preliminary results of miR-17-5p and miR-20a (key representatives of the miR-17-92 oncogenic cluster) expression analysis and their connection with signalling pathway activation in two of the most frequent paediatric tumours: medulloblastoma and ependymoma. Our study was performed using the microarray and qPCR techniques and showed PI3K/AKT/mTOR and RAS/MAPK/ERK among the forefront of the list of pathways with the largest number of genes involved in their activation compared to the control. Predicted target analysis indicated the agents from miR-17-92 cluster within miRNAs regulating activity of PI3K/AKT/mTOR and RAS/MAPK/ERK deregulated genes. The expression level of key representatives of the oncogenic cluster, miR-17-5p, and miR-20a, increased with the WHO grade of the analysed cases; the highest levels were found in medulloblastomas.
如今，分子研究对理解原发性脑肿瘤生物学、分类以及治疗方式的进展具有重要影响。在具有潜在治疗价值的新型生物标志物中，miRNAs（microRNAs）在某些情况下受到关注。miRNAs 是调节基因表达的小分子，包括编码参与信号通路的关键蛋白的基因，这些信号通路负责肿瘤形成过程中的生长和细胞存活。在脑肿瘤发生中异常激活的途径包括 PI3K/AKT/mTOR 和 RAS/MAPK/ERK 级联，与较差的预后和患者生存率降低有关。这项工作研究了个体 miRNAs 表达的变化与原发性脑肿瘤中 PI3K/AKT/mTOR 和 RAS/MAPK/ERK 信号通路调节基因之间的关系。在此，我们介绍了 miR-17-5p 和 miR-20a（miR-17-92 致癌簇的关键代表）表达分析的初步结果及其与两种最常见的儿科肿瘤：髓母细胞瘤和室管膜瘤中信号通路激活的关系。我们的研究使用了微阵列和 qPCR 技术，结果显示 PI3K/AKT/mTOR 和 RAS/MAPK/ERK 是参与其激活的基因数量最多的信号通路之一。预测靶标分析表明，miR-17-92 簇中的靶基因在调节 PI3K/AKT/mTOR 和 RAS/MAPK/ERK 活性的 miRNAs 中。致癌簇关键代表物 miR-17-5p 和 miR-20a 的表达水平随着分析病例的 WHO 分级而增加；在髓母细胞瘤中发现的水平最高。
