Exercise-associated microRNA programs as candidate modulators and biomarkers in glioblastoma: a narrative review

Abstract Glioblastoma Multiforme (GBM) remains one of the most challenging malignancies to treat due to its aggressive proliferation, resistance to apoptosis, extensive angiogenesis, and capacity to evade conventional therapies. MicroRNAs (miRNAs) act as critical post-transcriptional regulators of gene expression, modulating these pathogenic hallmarks. OncomiRs such as miR-10b, miR-221/222, and miR-21 promote tumorigenesis by enhancing cell survival, invasion, and drug resistance. Conversely, tumor-suppressor miRNAs (TS-miRNAs)—including miR-128, miR-34a, and miR-7—inhibit these malignant traits and are frequently downregulated in GBM. Emerging evidence suggests that physical exercise, a non-pharmacological intervention with systemic anti-cancer effects, can modulate the expression of miRNAs linked to tumor suppression and immune regulation. In other cancer models, exercise-induced miRNA alterations have been shown to disrupt signaling pathways governing proliferation, apoptosis, and stem cell maintenance, suggesting a potential therapeutic benefit in GBM. This study explores the hypothesis that exercise can favorably influence GBM biology by regulating oncogenic and tumor-suppressor miRNAs. By altering the tumor microenvironment and modifying circulating and tumor-intrinsic miRNA profiles, exercise may counteract key mechanisms of GBM progression and treatment resistance. Elucidating these miRNA-mediated effects could uncover novel biomarkers and provide a compelling rationale for integrating exercise into multimodal GBM treatment strategies.