Inhibition of glioblastoma cell invasion by hsa-miR-145-5p and hsa-miR-31-5p co-overexpression in human mesenchymal stem cells.
Cq = quantitation cycle
FBS = fetal bovine serum
FSCN1 = fascin actin-bundling protein 1
GBM = glioblastoma
GFP = green fluorescent protein
PBS = phosphate-buffered saline
PCR = polymerase chain reaction
cDNA = complementary DNA
delivery vehicle
glioma
hMSC = human bone marrow–derived mesenchymal stem cell
human bone marrow–derived mesenchymal stem cells
invasive ability
miRNA = microRNA
microRNA
oncology
α-MEM = alpha minimum essential medium
Journal
Journal of neurosurgery
ISSN: 1933-0693
Titre abrégé: J Neurosurg
Pays: United States
ID NLM: 0253357
Informations de publication
Date de publication:
01 01 2019
01 01 2019
Historique:
received:
10
01
2017
accepted:
28
08
2017
pubmed:
10
3
2018
medline:
19
10
2019
entrez:
10
3
2018
Statut:
ppublish
Résumé
Human bone marrow–derived mesenchymal stem cells (hMSCs) show tropism for brain tumors and may
be a useful vehicle for drug or gene delivery to malignant gliomas. Recently, some microRNAs (miRNAs) have been shown to suppress the invasiveness of malignant gliomas. To test their potential to become vehicles for the delivery of miRNA to malignant gliomas, hMSCs were
engineered so that hMSC secretion of miRNAs that inhibit glioma cell invasion was enabled without altering the hMSC tropism for glioma cells. In coculture, hMSCs cotransfected with hsa-miR-145-5p and -31-5p miRNAs showed markedly reduced
invasion by U87 glioma cells in a contact-dependent manner both in vitro and ex vivo, with invasion of hMSCs cotransfected with these 2 miRNAs by the U87 cells reduced to 60.7% compared with control cells. According to a Matrigel invasion assay, the tropism of the hMSCs for U87 cells was not affected. In glioma cell lines U251 and LN229, hMSCs exhibited tropism in vivo, and invasion of hMSCs cotransfected with hsa-miR-145-5p and -31-5p was also significantly less than that of control cells. When U87 cells were coimplanted into the striatum of organotypic rat brain slices with hMSCs cotransfected with hsa-miR-145 and -31-5p, the relative invasive area decreased by 37.1%; interestingly, these U87 cells showed a change to a rounded morphology that was apparent at the invasion front. Whole-genome microarray analysis of the expression levels of 58,341 genes revealed that the co-overexpression of hsa-miR-145-5p and -31-5p
downregulated FSCN1 expression in U87 cells. This study demonstrates that miRNA overexpression in hMSCs can alter the function of glioma cells
via contact-dependent transfer. Co-overexpression of multiple miRNAs may be a useful and novel therapeutic strategy. The study results suggest that hMSCs can be applied as a delivery vehicle for miRNAs.
Identifiants
pubmed: 29521593
pii: 2017.8.JNS1788
doi: 10.3171/2017.8.JNS1788
doi:
pii:
Substances chimiques
MIRN145 microRNA, human
0
MIRN31 microRNA, human
0
MicroRNAs
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM