| 1 | miR-182参与调节胶质母细胞瘤的凋亡、生长和分化(英文)显示文摘Glioblastoma multiforme(GBM)is a lethal,therapy-resistant brain cancer consisting of numerous tumor cell subpopulations,including stem-like glioma-initiating cells(GICs),which contribute to tumor recurrence following initial response to therapy.Here,we identified miR-182 as a regulator of apoptosis,growth,and differentiation programs whose expression level is correlated with GBM patient survival.Repression of Bcl2-like12(Bcl2L12),c-Met,and hypoxia-inducible factor 2α(HIF2A)is of central importance to miR-182 anti-tumor activity,as it results in enhanced therapy susceptibility,decreased GIC sphere size,expansion,and stemness in vitro.To evaluate the tumor-suppressive function of miR-182 in vivo,we synthesized miR-182-based spherical nucleic acids(182-SNAs);i.e.,gold nanoparticles covalently functionalized with mature miR-182 duplexes.Intravenously administered 182-SNAs penetrated the bloodbrain/blood-tumor barriers(BBB/BTB)in orthotopic GBM xenografts and selectively disseminated throughout extravascular glioma parenchyma,causing reduced tumor burden and increased animal survival.Our results indicate that harnessing the anti-tumor activities of miR-182 via safe and robust delivery of 182-SNAs represents a novel strategy for therapeutic intervention in GBM. | Kouri FM Hurley LA Daniel WL Day ES Hua Y Hao L Peng CY Merkel TJ Queisser MA Ritner C Zhang H James CD Sznajder JI Chin L Giljohann DA Kessler JA Peter ME Mirkin CA Stegh AH | 2015 | 中华神经外科疾病研究杂志2015，14，2： | 14 |
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