Roles of microRNAs carried by exosomes in glioblastoma microenvironment

Glioblastoma (GBM) is an extremely aggressive type of glioma affecting the central nervous system (CNS). Patient survival is typically less than one year and decreases with various mutations, deletions, and amplifications. The treatment of GBM is usually challenging since drug candidates that can cross the blood-brain barrier with low side effects are limited. The initial treatment for GBM involves surgical resection, followed by radiotherapy and administration of temozolomide (TMZ) as the primary adjuvant therapy. Following TMZ treatment, most patients experience tumor recurrence due to TMZ resistance within the first year. Given the intratumoral heterogeneity, elucidating the tumor microenvironment (TME) is paramount. Exosomes, a class of extracellular vesicles (EVs) released by cells into TME, are responsible for intercellular communication. The content of exosomes, originating from early endosomes and then from late endosomes, is exceptionally rich in oncogenic proteins, angiogenic factors, coding, and non-coding RNA, such as microRNAs (miRNAs). Exosomal miRNAs are critical in driving GBM pathogenesis. They contribute to disease progression, metastasis, cancer development, angiogenesis, and drug resistance. Additionally, exosomal miRNAs influence the cell migration, proliferation, and differentiation of glioma cells, making them potential biomarkers for diagnosis, prognosis, and therapeutic response prediction. This review discusses exosomal miRNA functions in GBM progression and highlights their potential clinical applications. Also, this review summarizes available databases for identifying exosome-associated miRNAs and exploring their functional roles in GBM.