RND1 inhibits epithelial-mesenchymal transition and temozolomide resistance of glioblastoma via AKT/GSK3-β pathway

Area of Science:

• Neuro-oncology
• Molecular Biology
• Cancer Research

Background:

• Glioblastoma (GBM) is a highly aggressive brain tumor.
• Resistance to temozolomide (TMZ) is a major challenge in GBM treatment, hindering clinical efficacy.
• Understanding the mechanisms of GBM invasion and TMZ resistance is crucial for developing effective therapies.

Purpose of the Study:

• To investigate the role of RND1 in GBM progression, invasion, and temozolomide (TMZ) resistance.
• To explore the association between RND1 and epithelial-mesenchymal transition (EMT) related genes.
• To evaluate RND1 as a potential therapeutic target for GBM.

Main Methods:

• Bioinformatic analysis to correlate RND1 with EMT-related genes.
• In vitro assays (colony formation, cell viability, Transwell, wound-healing) to assess cell growth and invasion.
• Western blot to analyze protein expression.
• In vivo studies in nude mice using RND1-targeted therapy combined with TMZ.

Main Results:

• RND1 overexpression suppressed GBM cell progression and migration, while RND1 knockdown promoted them.
• RND1 regulated GBM cell epithelial-mesenchymal transition (EMT) by inhibiting AKT and GSK3-β phosphorylation.
• RND1 significantly enhanced TMZ sensitivity in GBM cells both in vitro and in vivo.

Conclusions:

• RND1 overexpression inhibits GBM migration and EMT by downregulating the AKT/GSK3-β pathway.
• RND1 enhances the sensitivity of GBM cells to temozolomide (TMZ) therapy.
• Targeting RND1 presents a promising strategy for improving GBM treatment outcomes and overcoming TMZ resistance.