MicroRNA 199b-5p delivery through stable nucleic acid lipid particles (SNALPs) in tumorigenic cell lines.
MicroRNA (miR)-199b-5p has been shown to regulate Hes-1, a downstream effector of the canonical Notch and noncanonical SHH pathways, whereby it impairs medulloblastoma (MB) cancer stem cells (CSCs) through a decrease in the CD133+/CD15+ cell population. Here, we have developed stable nucleic acid lipid particles (SNALPs) that encapsulate miR-199b-5p. The efficacy of the miR-199b-5p delivery by these SNALPs is demonstrated by significant impairment of Hes-1 levels and CSC markers in a range of different tumorigenic cell lines: colon (HT-29, CaCo-2, and SW480), breast (MDA-MB231T and MCF-7), prostate (PC-3), glioblastoma (U-87), and MB (Daoy, ONS-76, and UW-228). After treatment with SNALP miR-199b-5p, there is also impairment of cell proliferation and no signs of apoptosis, as measured by caspases 3/7 activity and annexin V fluorescence cell sorter analyses. These data strengthen the importance of such carriers for miRNA delivery, which show no cytotoxic effects and provide optimal uptake into cells. Thus, efficient target downregulation in different tumorigenic cell lines will be the basis for future preclinical studies.
Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Federico II University of Naples, Naples, Italy.
Pasqualino
P
de Antonellis
Lucia
L
Liguori
Annarita
A
Falanga
Marianeve
M
Carotenuto
Veronica
V
Ferrucci
Immacolata
I
Andolfo
Federica
F
Marinaro
Immacolata
I
Scognamiglio
Antonella
A
Virgilio
Giuseppe
G
De Rosa
Aldo
A
Galeone
Stefania
S
Galdiero
Massimo
M
Zollo
D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D057809:HEK293 Cells; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes; D035683:MicroRNAs / Q000008:administration & dosage* / Q000737:chemistry
D008055:Lipids; D008081:Liposomes; D035683:MicroRNAs; C531408:mirn199 microRNA, human; D053148:Caspase 3; D053179:Caspase 7