# MiR 329/449 Suppresses Cell Proliferation, Migration and Synergistically Sensitizes GBM to TMZ by Inhibiting Src/FAK, NF-kB, and Cyclin D1 Activity

## TL;DR

This study shows that miR-329 and miR-449b can reduce GBM cell growth and migration and make the cancer more responsive to the drug TMZ.

## Contribution

The novel contribution is demonstrating that miR-329/449b synergistically enhances TMZ efficacy by inhibiting key signaling pathways in GBM cells.

## Key findings

- MiR-329/449b suppressed spheroid formation and migration of GBM cells.
- Combining miR-329/449b with TMZ enhanced TMZ's effects and inhibited NF-kB and Src/FAK pathways.
- The miR-TMZ combination is proposed as a viable therapy to improve GBM patient survival.

## Abstract

Glioblastoma Multiforme (GBM) is one of the most common brain tumors and is associated with aggressive tumor characteristics and extremely poor patient survival. The median survival time for GBM patients is around 12–15 months. Temozolomide (TMZ) is a key chemotherapeutic drug used in the treatment of GBM. However, at least 50% of GBM patients do not respond to TMZ, necessitating the identification of novel therapeutic strategies sensitizing patients to TMZ. In this study, we aimed to investigate the effects of two different tumor suppressor microRNAs (miR-329 and miR-449b) on cell proliferation and migration of GBM cells, and their potential for sensitizing GBM cells to TMZ. Our findings show that MiR-329/449b treatments suppressed spheroid formation and migration of GBM (LN229 and U87) cells. When miR treatments were combined with Temozolomide (TMZ), we also observed that they synergistically enhanced the suppressive effects of TMZ and inhibited the activity of clinically significant NF-KB and Src/FAK signaling pathways, making the combination therapy a viable option to treat GBM, with greater impact on patient survival.