Department of Pathology and Pathophysiology, Hunan Normal University School of Medicine, Changsha, 410013, China.
Department of Pathology, Xiangtan Central Hospital, Xiangtan, 411100, China.
Oncogene. 2019 Nov;38(47):7234-7248. doi: 10.1038/s41388-019-0922-3. Epub 2019 Sep 2.
Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. Currently, the prognosis of the patients with GBM is very poor and new molecular targets and treatment strategies are urgently needed to combat it. MicroRNA-148a (miR-148a) has been shown to be dysregulated in certain tumor types. However, the role of miR-148a in the pathogenesis of GBM is not fully understood. Here we comprehensively analyzed the roles of miR-148a, downstream DLGAP1, and their molecular pathways in GBM. We showed that miR-148a promote the proliferation and growth of GBM cells both in vitro and in vivo, and also induced the migration, invasion, and EMT (epithelial-mesenchymal transition) program of GBM cells by directly targeting DLGAP1. Furthermore, we identified 31 new miR-148a targets and found that miR-148a function was mainly involved in the cell adhesion signaling pathway and was associated with nervous system diseases. Our findings provide a new mechanism for miR-148a-mediated GBM cell invasion and reveal previously unreported targets of miR-148a as well as novel miR-148a-mediated regulatory networks in GBM. These results increase the understanding of the role of miR-148a in GBM and may lead to novel therapeutic strategies for GBM.
胶质母细胞瘤(GBM)是成人中最常见的恶性原发性脑肿瘤。目前,GBM 患者的预后非常差,急需新的分子靶点和治疗策略来对抗它。miR-148a(miR-148a)在某些肿瘤类型中已被证明失调。然而,miR-148a 在 GBM 发病机制中的作用尚不完全清楚。在这里,我们全面分析了 miR-148a、下游 DLGAP1 及其分子途径在 GBM 中的作用。我们表明,miR-148a 可在体外和体内促进 GBM 细胞的增殖和生长,并通过直接靶向 DLGAP1 诱导 GBM 细胞的迁移、侵袭和 EMT(上皮-间充质转化)程序。此外,我们鉴定了 31 个新的 miR-148a 靶标,并发现 miR-148a 的功能主要涉及细胞黏附信号通路,并与神经系统疾病有关。我们的研究结果为 miR-148a 介导的 GBM 细胞侵袭提供了新的机制,并揭示了 miR-148a 的以前未报道的靶标以及 GBM 中新型 miR-148a 介导的调节网络。这些结果增加了对 miR-148a 在 GBM 中作用的理解,并可能为 GBM 提供新的治疗策略。