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

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.

Tumor-derived exosomal microRNA-7-5p enhanced by verbascoside inhibits biological behaviors of glioblastoma in vitro and in vivo

“…Accordingly, VB has been demonstrated to repress GBM cell viability, invasion, migration, and tumor growth while promoting GBM cell apoptosis by increasing let-7g-5p expression and inhibiting high-mobility group (HMG)A2 expression. 28 Our study findings demonstrated that miR-7-5p was poorly expressed in GBM, and the administration with VB induced the secretion of exosomal miR-7-5p, which could consequently exercise an inhibitory effect on GBM cell proliferation, invasion, migration, and vessel-like tube formation. Currently, miR-7-5p has been highlighted to function as a tumor suppressor involved in various cancers, including GBM.…”

Association of HMGA2 Polymorphisms with Glioma Susceptibility in Chinese Children

“…HMGA2 is suppressed by let-7g-5p and down-regulation of HMGA2 expression can promote GBM tumor cell apoptosis and inhibit their invasion, indicating that HMGA2 is a potential novel target gene in GBM. 36 In addition, HMGA2 can be targeted by miR-370-3p , which inhibits glioma cell growth and invasion 37 and is, therefore, a potential target for glioma therapy.…”

Systematic analysis of the long noncoding RNA (lncRNA)-miRNA-mRNA competing endogenous RNA network to identify prognostic biomarkers and the potential regulatory axis in glioblastoma multiforme

“…Multiple studies have validated that targeting HMGA2 in GBM may be therapeutically beneficial. High expression of HMGA2 in GBM has been confirmed to promote GBM cell viability, invasion, migration, stemness and tumor growth, inhibit cell apoptosis and autophagy ( 37 , 38 ), and be involved in the double-strand break repair pathway ( 39 ). LINC00336, despite the lack of any study in GBM, has been identified to be significantly correlated with renal cell carcinoma OS ( 40 ), and its overexpression may promote lung cancer cell growth, colony formation, and tumor formation, and inhibit ferroptosis ( 41 ).…”