Abstract 2788: Targeting miR-92b reduces neurosphere formation in glioblastoma cancer stem cells

Abstract Glioblastoma (GBM) is a grade IV brain tumor with a dismal prognosis, driven by aggressive brain tumor-initiating cells (BTICs). This study focuses on targeting microRNA-92b-3p (miR-92b-3p), a microRNA aberrantly overexpressed in GBM that correlates with poor patient outcomes. We utilized primary BTIC neurospheres M1123 and GBM1A, derived from GBM patients, to investigate miR-92b-3p's role in tumor progression and therapeutic resistance. Our findings revealed a striking 40-fold higher basal expression of miR-92b-3p in GBM1A compared to M1123. Functional studies showed that miR-92b-3p inhibition significantly disrupted neurosphere formation in both cell lines up to 96 hours post-transfection, highlighting its essential role in maintaining GBM stemness. Additionally, the IC50 values for temozolomide, the standard GBM chemotherapeutic agent, were 27 µM for M1123 and 30 µM for GBM1A, suggesting similar baseline resistance. Ongoing experiments are exploring whether miR-92b-3p inhibition sensitizes BTICs to temozolomide, potentially enhancing its efficacy. These results underscore miR-92b-3p’s critical role in neurosphere maintenance and chemoresistance in GBM cancer stem cells. Its overexpression may serve as a biomarker for aggressive tumor behavior, and its inhibition represents a promising therapeutic strategy to target BTICs, disrupt GBM progression, and improve patient outcomes. Citation Format: Annelis O. Sánchez-Álvarez, Diego García-Ortiz, Misael Rivera-García, Alanis M. Labeaga-Sainz, Pablo E. Vivas-Mejia. Targeting miR-92b reduces neurosphere formation in glioblastoma cancer stem cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2788.