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

Glioblastoma Multiforme (GBM) is the most common brain tumors that 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 the patients to TMZ. In this study we aimed to investigate effects of two different tumor suppressor microRNAs (miR-329 and miR-449b) on cell proliferation and migration of GBM cells their potential for sensitizing GBM cells to TMZ. Our findings MiR-329/449b treatments suppressed spheroid formation and migration of GBM (LN229 and U87) cells. When miR treatments were combined with Temozolomide (TMZ) we observed that they synergistically enhanced the suppressive effects of TMZ and inhibited the activity of clinically significant NF-KB Src/FAK signaling pathways making the combination therapy as a viable option to treat GBM with greater impact on patient survival.