Glioblastoma (GBM) is an aggressive brain tumor that develops from neuroglial stem cells and represents a highly heterogeneous group of neoplasms. These tumors are predominantly correlated with a dismal prognosis and poor quality of life. In spite of major advances in developing novel and effective therapeutic strategies for patients with glioblastoma, multidrug resistance (MDR) is considered to be the major reason for treatment failure. Several mechanisms contribute to MDR in GBM, including upregulation of MDR transporters, alterations in the metabolism of drugs, dysregulation of apoptosis, defects in DNA repair, cancer stem cells, and epithelial–mesenchymal transition. MicroRNAs (miRNAs) are a large class of endogenous RNAs that participate in various cell events, including the mechanisms causing MDR in glioblastoma. In this review, we discuss the role of miRNAs in the regulation of the underlying mechanisms in MDR glioblastoma which will open up new avenues of inquiry for the treatment of glioblastoma.

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