Glioblastoma (GBM) is among the most lethal human cancers, being generally characterized by rapid diffuse
and infiltrative growth and high level of cellular heterogeneity associated with therapeutic resistance. Despite remarkable
advances in cancer theranostics, which resulted in significant improvement of clinical outcomes, patient survival remains
under one year. In recent years, considerable progress has been made in understanding the role of small non-coding
RNAs, designated microRNAs, in the pathogenesis of GBM. Indeed, microRNAs were found to play a critical role in
multiple steps of the tumorigenic process, including cellular proliferation, apoptosis evasion, invasion, angiogenesis, and
stemness. Moreover, the modulation of microRNA expression, using either antisense oligonucleotides or precursor/mimic
sequences, revealed a tremendous potential for application in GBM-targeted therapeutic approaches, either per se or in
combination with chemo- and/or radiotherapy.
In this manuscript, we review the regulatory role of microRNAs in key cellular processes underlying GBM tumorigenesis,
including migration and invasion, apoptosis evasion, angiogenesis and GBM stem-like cell proliferation/differentiation,
and discuss the current knowledge on their potential as diagnostic, prognostic and predictive biomarkers in this disease.
We also address the latest advances in microRNA-based therapeutic approaches for GBM, by summarizing the major
achievements in in vitro and pre-clinical studies. The trends identified by these studies are highlighted in order to provide
new prospects for future developments towards the successful treatment of GBM.