LAUSR

MicroRNA (miRNA) dysregulation plays a central role in the initiation, progression, and drug resistance of virtually all cancer types. MiRNA-based therapies are a promising therapeutic modality against most malignancies. MiR-92b is aberrantly abundant in glioblastoma (GBM), the most aggressive and mortal of all primary brain tumors. Thus, miR-92b is a potential target for GBM therapy. First, it is critically important to assess the molecular mechanism of miR-92b regulation in GBM cells. In this study, we investigated the molecular and biological effects of targeting miR-92b in GBM cells with oligonucleotide miRNA inhibitors (OMIs). Incubation of GBM cells with miR-92b-OMIs resulted in decreased cell proliferation and reduction in cell migration. MiR-92b inhibition also promoted apoptosis as assessed by caspase-3 activation. Bioinformatics and real-time PCR studies identified several miR-92b target genes in GBM cells. Western blot analysis and luciferase reporter assays confirmed F-Box and WD Repeat Domain Containing 7 (FBXW7) as a direct miR-92b target gene in GBM cells. FBXW7 is one of ~70 F-BOX proteins in humans particularly studied in cancer due to its role in the ubiquitylation of positive regulators; also known as accelerators of the cell cycle (i.e. the oncogene c-Myc). Thus, an increase in FBXW7 promoted the decrease of c-MYC protein levels in GBM cells. These findings indicate that targeting miR-92b inhibits GBM cell proliferation by increasing the levels of tumor suppressor genes in charge of protein ubiquitination. Citation Format: Annelis Odette Sanchez-Alvarez, Nilmary Grafals-Ruiz, Yasmarie Santana-Rivera, Fatma Valiyeva, Nathaly M. Rosado-Rivera, Pablo E. Vivas-Mejía. MiR-92b targets FBXW7 in GBM cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2538.