Abstract
Glioblastoma (GB) is the most aggressive form of brain cancer in adults, characterized by poor survival rates and lack of effective therapies. MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression post-transcriptionally through specific pairing with target messenger RNAs (mRNAs). Extracellular vesicles (EVs), a heterogeneous group of cell-derived vesicles, transport miRNAs, mRNAs and intracellular proteins, and have been shown to promote horizontal malignancy into adjacent tissue, as well as resistance to conventional therapies. Furthermore, GB-derived EVs have distinct miRNA contents and are able to penetrate the blood–brain barrier. Numerous studies have attempted to identify EV-associated miRNA biomarkers in serum/plasma and cerebrospinal fluid, but their collective findings fail to identify reliable biomarkers that can be applied in clinical settings. However, EVs carrying specific miRNAs or miRNA inhibitors have great potential as therapeutic nanotools in GB, and several studies have investigated this possibility on in vitro and in vivo models. In this review, we discuss the role of EVs and their miRNA content in GB progression and resistance to therapy, with emphasis on their potential as diagnostic, prognostic and disease monitoring biomarkers and as nanocarriers for gene therapy.
Highlights
Glioblastoma (GB) is the most aggressive form of brain cancer in adults, characterized by fast growth and invasiveness, high tumor heterogeneity, poor survival and lack of effective therapies [1,2,3]
The latest classification of central nervous system (CNS) tumors released by the World Health Organization (WHO) [4] takes into account molecular markers along with histological assessment and clinical presentation into the diagnosis and classification of GB
Despite some results reported in the literature, occupational exposure to extremely low frequency magnetic fields is not considered as a GB risk factor by the International Agency for Research on Cancer (IARC) [80]
Summary
Glioblastoma (GB) is the most aggressive form of brain cancer in adults, characterized by fast growth and invasiveness, high tumor heterogeneity, poor survival and lack of effective therapies [1,2,3]. This, combined with the fact that miRNAs are relatively easy to measure in biological fluids, supports their potential use as biomarkers for diagnosis, prognosis and therapeutic response monitoring of CNS malignancies. EVs have been shown to contain a significantly distinct miRNA signature compared to their cells of origin, suggesting a selective miRNA packaging into EVs [24], and their number and miRNA content change under pathological conditions [23,44,45] These aspects could be exploited in a clinical setting as EVs have been shown to have diagnostic potential in various pathologies, including GB [26,46], as well as biomarker potential for treatment response monitoring and disease recurrence [47,48,49,50,51,52]. We highlight the main aspects of GB pathology, including cellular and molecular insights into disease progression, the properties and role of EVs in GB progression and the potential of EV-associated miRNAs as biomarkers and therapeutic tools in GB
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