Dataset Information

Inhibition of human glioblastoma invasion and growth upon co-administration of a synergic miRNA pool actuated in vivo by nanocarriers

ABSTRACT: Although small interfering RNAs are being routinely used in the clinic, the therapeutic potential of oncogene co-regulation via multiple microRNAs (miRNAs) is still vastly underexplored. Here, the functional synergism of a pool of 11 miRNAs, which are involved in neural stem cell differentiation, was investigated in 3 different patient-derived GBM clones as well as in a conventional orthotopic mouse model of human GBM. First, we confirmed that the 11 miRNAs are mostly downregulated in all tested human GBM cells. Then, we demonstrated that the modulation of the 11-miRNA pool affected the expression of proteins involved in tumor cell adhesion and glioma stemness. These findings positively correlate with a significant reduction in cancer cell invasiveness, which was documented in both cell monolayer and tumor spheroid assays. Notably, a single miRNA of the 11 (i.e., miR-124) cannot recapitulate the functional synergism documented with the pool. Moreover, the 11 miRNAs downregulated an identical subset of proteins in different patient-derived GBM cells, several of them involved in the Collagen pathway, that correlate with the malignancy grade and subtype, further supporting the ability of the selected pool to modulate tumor aggressiveness. Finally, the 11-miRNA pool was efficiently encapsulated into Apolipoprotein E-coated lipid nanoparticles and deposited in orthotopic murine models of human GBM. A single nanoparticle administration significantly impaired tumor growth and extended survival by >50% compared to control experiments, without inducing any visible adverse effect. This study highlights the role of miRNAs’ functional synergism in treating malignancies with dismal prognosis and proves that nanomedicines can be used to effectively deliver multiple, different miRNAs in vivo, possibly in combination with chemotherapeutic drugs.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Dendritic Cell, Cell Culture

DISEASE(S): Brain Glioblastoma Multiforme

SUBMITTER: Andrea Armirotti

LAB HEAD: Andrea Armirotti

PROVIDER: PXD020335 | Pride | 2026-01-05

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	CB_16Aug2018_GBM1CTRn1.wiff	Wiff
	CB_16Aug2018_GBM1CTRn1.wiff.scan	Wiff
	CB_16Aug2018_GBM1CTRn2.wiff	Wiff
	CB_16Aug2018_GBM1CTRn2.wiff.scan	Wiff
	CB_16Aug2018_GBM1CTRn3.wiff	Wiff

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Publications

Synergic microRNAs suppress human glioblastoma progression by modulating clinically relevant targets.

Rancati Silvia S Pereira Rui C RC Schlich Michele M Sgroi Stefania S Beatini Silvia S La Rosa Letizia L Giantomasi Lidia L Pelizzoli Roberta R Braccia Clarissa C Di Fonzo Andrea A Spattini Carlotta C Tuntevski Kiril K Lo Van Amanda A Pons-Espinal Meritxell M Palange Annalisa A Bajetto Adriana A Daga Antonio A Armirotti Andrea A Florio Tullio T Decuzzi Paolo P De Pietri Tonelli Davide D

Molecular therapy. Nucleic acids 20251120 4

Glioblastoma (GBM) is a highly aggressive brain tumor characterized by therapy-resistant glioma stem-like cells (GSCs) and extensive infiltration into surrounding brain tissue. MicroRNAs (miRNAs) are pleiotropic post-transcriptional regulators of oncogenic pathways, but their tumor-suppressive function is frequently lost in GBM. This study explores a multimodal therapeutic approach by restoring a combination of miRNAs to exploit their synergistic effects against GBM. Using patient-derived GBM ce ...[more]

PMID: 41467122

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