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
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

Pagination

44-55

Auteurs

Ryota Kurogi (R)

Departments of1Neurosurgery and.
2Department of Neurosurgery, National Hospital Organization, Clinical Research Institute, Kyushu Medical Center, Fukuoka, Japan.

Akira Nakamizo (A)

Departments of1Neurosurgery and.
2Department of Neurosurgery, National Hospital Organization, Clinical Research Institute, Kyushu Medical Center, Fukuoka, Japan.

Satoshi O Suzuki (SO)

3Neuropathology, Graduate School of Medical Sciences, Kyushu University; and.

Masahiro Mizoguchi (M)

Departments of1Neurosurgery and.

Koji Yoshimoto (K)

Departments of1Neurosurgery and.

Toshiyuki Amano (T)

Departments of1Neurosurgery and.

Takeo Amemiya (T)

Departments of1Neurosurgery and.

So Takagishi (S)

Departments of1Neurosurgery and.

Koji Iihara (K)

Departments of1Neurosurgery and.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH