Verbascoside inhibits progression of glioblastoma cells by promoting Let-7g-5p and down-regulating HMGA2 via Wnt/beta-catenin signalling blockade

毛蕊花苷通过阻断 Wnt/β-catenin 信号促进 Let-7g-5p 并下调 HMGA2 来抑制胶质母细胞瘤细胞的进展

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作者:Wei-Qiang Jia, Jian-Wei Zhu, Cheng-Yong Yang, Jun Ma, Tian-You Pu, Guo-Qiang Han, Ming-Ming Zou, Ru-Xiang Xu

Abstract

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.

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