Crossroads of cell fate: miR-34-mediated regulation of apoptosis and autophagy in glioblastoma

Glioblastoma (GBM) is the most aggressive and treatment-resistant form of primary brain tumor, characterized by rapid proliferation, extensive heterogeneity, and evasion of programmed cell death. Among emerging molecular regulators, microRNA-34 (miR-34) has gained attention as a potent tumor suppressor with the ability to modulate key signaling pathways involved in cell survival and death. This review explores the dual role of miR-34 in orchestrating apoptosis and autophagy, two fundamental processes that determine glioblastoma cell fate. We summarize current findings on how miR-34 directly targets genes involved in apoptotic signaling-such as BCL2, SIRT1, and NOTCH1-thereby promoting cell death and sensitizing GBM cells to therapeutic agents. Additionally, we highlight the context-dependent influence of miR-34 on autophagic flux, where it can either facilitate cytoprotective responses or trigger autophagy-associated cell death. Understanding this regulatory balance provides insight into the cellular plasticity of GBM and opens new avenues for therapeutic intervention. Targeting miR-34 or its downstream pathways offers promising potential to overcome resistance mechanisms and improve outcomes in glioblastoma treatment.

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