Department of Neurosurgery, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
Department of Neurosurgery, Guizhou Provincial People's Hospital, Guiyang, China.
J Cell Mol Med. 2020 Mar;24(5):2901-2916. doi: 10.1111/jcmm.14884. Epub 2020 Jan 30.
Glioblastoma (GBM) continues to show a poor prognosis despite advances in diagnostic and therapeutic approaches. The discovery of reliable prognostic indicators may significantly improve treatment outcome of GBM. In this study, we aimed to explore the function of verbascoside (VB) in GBM and its effects on GBM cell biological processes via let-7g-5p and HMGA2. Differentially expressed GBM-related microRNAs (miRNAs) were initially screened. Different concentrations of VB were applied to U87 and U251 GBM cells, and 50 µmol/L of VB was selected for subsequent experiments. Cells were transfected with let-7g-5p inhibitor or mimic, and overexpression of HMGA2 or siRNA against HMGA2 was induced, followed by treatment with VB. The regulatory relationships between VB, let-7g-5p, HMGA2 and Wnt/β-catenin signalling pathway were determined. The results showed that HMGA2 was a direct target gene of let-7g-5p. VB treatment or let-7g-5p overexpression inhibited HMGA2 expression and the activation of Wnt/β-catenin signalling pathway, which further inhibited cell viability, invasion, migration, tumour growth and promoted GBM cell apoptosis and autophagy. On the contrary, HMGA2 overexpression promoted cell viability, invasion, migration, tumour growth while inhibiting GBM cell apoptosis and autophagy. We demonstrated that VB inhibits cell viability and promotes cell autophagy in GBM cells by up-regulating let-7g-5p and down-regulating HMGA2 via Wnt/β-catenin signalling blockade.
尽管在诊断和治疗方法上取得了进展，但胶质母细胞瘤（GBM）的预后仍然很差。发现可靠的预后指标可能会显著改善 GBM 的治疗效果。在这项研究中，我们旨在通过 let-7g-5p 和 HMGA2 来探索毛蕊花糖苷（VB）在 GBM 中的作用及其对 GBM 细胞生物学过程的影响。最初筛选了差异表达的 GBM 相关 microRNAs（miRNAs）。将不同浓度的 VB 应用于 U87 和 U251 GBM 细胞，选择 50 μmol/L 的 VB 用于后续实验。用 let-7g-5p 抑制剂或模拟物转染细胞，并诱导 HMGA2 过表达或针对 HMGA2 的 siRNA，然后用 VB 处理。确定 VB、let-7g-5p、HMGA2 和 Wnt/β-catenin 信号通路之间的调节关系。结果表明，HMGA2 是 let-7g-5p 的直接靶基因。VB 处理或 let-7g-5p 过表达抑制 HMGA2 表达和 Wnt/β-catenin 信号通路的激活，从而进一步抑制细胞活力、侵袭、迁移、肿瘤生长并促进 GBM 细胞凋亡和自噬。相反，HMGA2 过表达促进了细胞活力、侵袭、迁移、肿瘤生长，同时抑制了 GBM 细胞凋亡和自噬。我们证明 VB 通过上调 let-7g-5p 和下调 HMGA2 来抑制 GBM 细胞活力并促进细胞自噬，通过 Wnt/β-catenin 信号通路阻断。
