MicroRNA-21 inhibition enhances in vitro chemosensitivity of temozolomide-resistant glioblastoma cells

Abstract

BACKGROUND: Glioblastoma multiforme (GBM) is a form of highly malignant brain tumour. Temozolomide (TMZ) is the standard agent for GBM, but TMZ-resistance is common and accounts for many treatment failures. MicroRNA-21 (miR-21) is a non-coding RNA that plays critical roles in many biological processes in cancer, including chemoresistance. We investigated miR-21 expression and the effect of miR-21 inhibition in GBM with acquired TMZ resistance. MATERIALS AND METHODS: Human GBM cell line D54MG was treated with TMZ chronically to develop a chemoresistant subclone. MiR-21 inhibition was achieved by transfection with anti-mir-21 oligonucleotide. RESULTS: Chronic TMZ exposure resulted in acquired TMZ-resistance and elevated miR-21 expression. Concomitant treatment with miR-21 inhibitor and TMZ resulted in a significantly higher apoptotic rate than TMZ treatment alone. CONCLUSION: MiR-21 may have a potential for use as a biomarker of acquired TMZ resistance. MiR-21 inhibition can be further explored as a potential chemotherapy adjunct in the treatment of TMZ-resistant GBM.