Laboratory for Human Molecular Genetics, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
Cellular Oncology Group, Biodonostia Health Research Institute, San Sebastian, Spain.
Cell Oncol (Dordr). 2019 Feb;42(1):41-54. doi: 10.1007/s13402-018-0405-5. Epub 2018 Sep 12.
Glioblastoma is the most common and lethal adult brain tumor. Despite current therapeutic strategies, including surgery, radiation and chemotherapy, the median survival of glioblastoma patients is 15 months. The development of this tumor depends on a sub-population of glioblastoma stem cells governing tumor propagation and therapy resistance. SOX3 plays a role in both normal neural development and carcinogenesis. However, little is known about its role in glioblastoma. Thus, the aim of this work was to elucidate the role of SOX3 in glioblastoma.
SOX3 expression was assessed using real-time quantitative PCR (RT-qPCR), Western blotting and immunohistochemistry. MTT, immunocytochemistry and Transwell assays were used to evaluate the effects of exogenous SOX3 overexpression on the viability, proliferation, migration and invasion of glioblastoma cells, respectively. The expression of Hedgehog signaling pathway components and autophagy markers was assessed using RT-qPCR and Western blot analyses, respectively.
Higher levels of SOX3 expression were detected in a subset of primary glioblastoma samples compared to those in non-tumoral brain tissues. Exogenous overexpression of this gene was found to increase the proliferation, viability, migration and invasion of glioblastoma cells. We also found that SOX3 up-regulation was accompanied by an enhanced activity of the Hedgehog signaling pathway and by suppression of autophagy in glioblastoma cells. Additionally, we found that SOX3 expression was elevated in patient-derived glioblastoma stem cells, as well as in oncospheres derived from glioblastoma cell lines, compared to their differentiated counterparts, implying that SOX3 expression is associated with the undifferentiated state of glioblastoma cells.
From our data we conclude that SOX3 can promote the malignant behavior of glioblastoma cells.
胶质母细胞瘤是最常见和最致命的成人脑肿瘤。尽管目前有包括手术、放疗和化疗在内的治疗策略，但胶质母细胞瘤患者的中位生存期为 15 个月。这种肿瘤的发展依赖于一小部分胶质母细胞瘤干细胞，这些干细胞控制着肿瘤的增殖和对治疗的耐药性。SOX3 在正常神经发育和癌变中都发挥作用。然而，关于其在胶质母细胞瘤中的作用知之甚少。因此，本研究旨在阐明 SOX3 在胶质母细胞瘤中的作用。
采用实时定量 PCR（RT-qPCR）、Western blot 和免疫组织化学法评估 SOX3 的表达。MTT、免疫细胞化学和 Transwell 测定分别用于评估外源性 SOX3 过表达对胶质母细胞瘤细胞活力、增殖、迁移和侵袭的影响。采用 RT-qPCR 和 Western blot 分析分别评估 Hedgehog 信号通路成分和自噬标志物的表达。
与非肿瘤性脑组织相比，在一部分原发性胶质母细胞瘤样本中检测到更高水平的 SOX3 表达。该基因的过表达被发现增加了胶质母细胞瘤细胞的增殖、活力、迁移和侵袭。我们还发现，SOX3 上调伴随着 Hedgehog 信号通路活性的增强和胶质母细胞瘤细胞自噬的抑制。此外，我们发现 SOX3 在患者来源的胶质母细胞瘤干细胞以及源自胶质母细胞瘤细胞系的类器官中表达升高，与分化细胞相比，这表明 SOX3 表达与胶质母细胞瘤细胞的未分化状态有关。
从我们的数据中我们得出结论，SOX3 可以促进胶质母细胞瘤细胞的恶性行为。
